query: the mhc class 1 molecule is recognized by which cell type

pos: MHC class I MHC class I MHC class I molecules are one of two primary classes of major histocompatibility complex (MHC) molecules (the other being MHC class II) and are found on the cell surface of all nucleated cells in the bodies of jawed vertebrates. They also occur on platelets, but not on red blood cells. Their function is to display peptide fragments of non-self proteins from within the cell to cytotoxic T cells; this will trigger an immediate response from the immune system against a particular non-self antigen displayed with the help of an MHC class I protein. Because MHC class I

pos: Adaptive immune system pathogens), or are otherwise damaged or dysfunctional. Naive cytotoxic T cells are activated when their T-cell receptor (TCR) strongly interacts with a peptide-bound MHC class I molecule. This affinity depends on the type and orientation of the antigen/MHC complex, and is what keeps the CTL and infected cell bound together. Once activated, the CTL undergoes a process called clonal selection, in which it gains functions and divides rapidly to produce an army of “armed” effector cells. Activated CTL then travels throughout the body searching for cells that bear that unique MHC Class I + peptide. When exposed to these infected

pos: Antigen presentation of MHC molecules which differ in the of the antigens: MHC class I molecules (MHC-I) bind peptides from the cell cytosol, while peptides generated in the endocytic vesicles after internalisation are bound to MHC class II (MHC-II). Cellular membranes separate these two cellular environments - intracellular and extracellular. Each T cell can finally recognise only ten to hundreds copies of a unique sequence of a single peptide among thousands of other peptides presented on the very same cell because MHC molecule in one cell can bind quite a large range of peptides. Cytotoxic T cells (also known as T, killer

pos: MHC class I molecules present peptides derived from cytosolic proteins, the pathway of MHC class I presentation is often called "cytosolic" or "endogenous pathway". In humans, the HLAs corresponding to MHC class I are HLA-A, HLA-B, and HLA-C. Class I MHC molecules bind peptides generated mainly from degradation of cytosolic proteins by the proteasome. The MHC I:peptide complex is then inserted via endoplasmic reticulum into the external plasma membrane of the cell. The epitope peptide is bound on extracellular parts of the class I MHC molecule. Thus, the function of the class I MHC is to display intracellular proteins to cytotoxic T cells

pos: Cytotoxic T cell Cytotoxic T cell A cytotoxic T cell (also known as T, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected (particularly with viruses), or cells that are damaged in other ways. Most cytotoxic T cells express T-cell receptors (TCRs) that can recognize a specific antigen. An antigen is a molecule capable of stimulating an immune response, and is often produced by cancer cells or viruses. Antigens inside a cell are bound to class I MHC molecules,

pos: Antigen-presenting cell B cell marker CD40 binds to CD40L on the T cell surface. When activated by a T cell, a B cell can undergo antibody isotype switching, affinity maturation, as well as formation of memory cells. Non-professional antigen presenting cells include all nucleated cell types in the body. They use an MHC class I molecule coupled to beta-2 microglobulin to display endogenous peptides on the cell membrane. These peptides originate within the cell itself, in contrast to the exogenous antigen displayed by professional APCs using MHC class II molecules. Cytotoxic T cells are able to interact with endogenous antigen presented using

pos: CD8 CD8 CD8 (cluster of differentiation 8) is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor (TCR). Like the TCR, CD8 binds to a major histocompatibility complex (MHC) molecule, but is specific for the class I MHC protein. There are two isoforms of the protein, alpha and beta, each encoded by a different gene. In humans, both genes are located on chromosome 2 in position 2p12. The CD8 co-receptor is predominantly expressed on the surface of cytotoxic T cells, but can also be found on natural killer cells, cortical thymocytes, and dendritic cells.The CD8 molecule is

pos: Artificial antigen presenting cells which is loaded with the specific antigen. MHC class I are found on all cells and stimulate cytotoxic T cells (CD8 cells), and MHC class II are found on APCs and stimulate helper T cells (CD4 cells). It is the specific antigen or epitope that is loaded into the MHC determines the antigen-specificity. The peptide-loaded MHC engages with the cognate T cell receptor (TCR) found on the T cells. T cells need another signal to become activated in addition to Signal 1, this is done by co-stimulatory molecules such as the proteins CD80 (B7.1) or CD86 (B7.2), although other additional

pos: Natural killer cell I alleles, which could explain why NK cells preferentially kill cells that possess low levels of MHC class I molecules. This mode of NK cell target interaction is known as "missing-self recognition", a term coined by Klas Kärre and co-workers in the late 90s. MHC class I molecules are the main mechanism by which cells display viral or tumor antigens to cytotoxic T cells. A common evolutionary adaptation to this is seen in both intracellular microbes and tumors: the chronic down-regulation of MHC I molecules, which makes affected cells invisible to T cells, allowing them to evade T cell-mediated immunity.

pos: Antigen-presenting cell been processed and presented by cells via carrier molecules like MHC molecules. Helper T cells can recognize exogenous antigen presented on MHC class II; cytotoxic T cells can recognize endogenous antigen presented on MHC class I. Most cells in the body can present antigen to CD8+ cytotoxic T cells via MHC class I ; however, the term "antigen-presenting cell" is often used specifically to describe professional APCs. Such cells express MHC class I and MHC class II molecules and can stimulate CD4+ helper T cells as well as cytotoxic T cells. APCs can also present foreign and self lipids to

neg: Cytotoxic T cell and brought to the surface of the cell by the class I MHC molecule, where they can be recognized by the T cell. If the TCR is specific for that antigen, it binds to the complex of the class I MHC molecule and the antigen, and the T cell destroys the cell. In order for the TCR to bind to the class I MHC molecule, the former must be accompanied by a glycoprotein called CD8, which binds to the constant portion of the class I MHC molecule. Therefore, these T cells are called CD8+ T cells. The affinity between CD8

neg: Major histocompatibility complex takes up an antigenic protein, performs antigen processing, and returns a molecular fraction of it—a fraction termed the epitope—and displays it on the APC's surface coupled within an MHC class II molecule (antigen presentation). On the cell's surface, the epitope can be recognized by immunologic structures like T cell receptors (TCRs). The molecular region which binds to the epitope is the paratope. On surfaces of helper T cells are CD4 receptors, as well as TCRs. When a naive helper T cell's CD4 molecule docks to an APC's MHC class II molecule, its TCR can meet and be imprinted by the

neg: CD4+ T cells and antitumor immunity molecules, to CD8 T cells, and not expressed on the cell surface bound to MHC class II molecules, which is required for presentation to CD4 T cells. Research has shown that the two pathways by which antigens are presented cross over in the endoplasmic reticulum of the cell, in which MHC class I, MHC class II and endogenously synthesized antigenic proteins are all present. These antigen proteins are prevented from binding to MHC class II molecules by a protein known as the invariant chain or Ii, which, in a normal cell, remains bound to the MHC class II molecule until

neg: Polyclonal B cell response with MHC class I molecules. An alternate pathway of endocytic processing had also been demonstrated wherein certain proteins like fibrinogen and myoglobin can bind as a whole to MHC-II molecules after they are denatured and their disulfide bonds are reduced (breaking the bond by adding hydrogen atoms across it). The proteases then degrade the exposed regions of the protein-MHC II-complex. After the processed antigen (peptide) is complexed to the MHC molecule, they both migrate together to the cell membrane, where they are exhibited (elaborated) as a complex that can be recognized by the CD 4+ (T helper cell) – a

neg: Antigen-presenting cell T cells and NK cells by using the CD1 family of proteins, which are structurally similar to the MHC class I family. Professional APCs specialize in presenting antigen to T cells. They are very efficient at internalizing antigens, either by phagocytosis (macrophages and dendritic cells) or by receptor-mediated endocytosis (B cells), processing the antigen into peptide fragments and then displaying those peptides, bound to a class II MHC molecule, on their membrane. The T cell recognizes and interacts with the antigen-class II MHC molecule complex on the membrane of the antigen-presenting cell. An additional co-stimulatory signal is then produced by

neg: MHC class II fragment known as CLIP which maintains blockage of the peptide binding cleft on the MHC molecule. An MHC class II-like structure, HLA-DM, facilitates CLIP removal and allows the binding of peptides with higher affinities. The stable class II MHC is then presented on the cell surface. After MHC class II complexes are synthesized and presented on APCs they are unable to be expressed on the cell surface indefinitely, due to the internalization of the plasma membrane by the APCs. In some cells, antigens bind to recycled MHC class II molecules while they are in the early endosomes. While other cells

neg: Major histocompatibility complex proteins within the cell. The MHC gene family is divided into three subgroups: class I, class II, and class III. Class I MHC molecules have β2 subunits so can only be recognised by CD8 co-receptors. Class II MHC molecules have β1 and β2 subunits and can be recognised by CD4 co-receptors. In this way MHC molecules chaperone which type of lymphocytes may bind to the given antigen with high affinity, since different lymphocytes express different T-Cell Receptor (TCR) co-receptors. Diversity of antigen presentation, mediated by MHC classes I and II, is attained in at least three ways: (1) an organism's

neg: Major histocompatibility complex to killer T cells, also called cytotoxic T lymphocytes (CTLs). A CTL expresses CD8 receptors, in addition to TCRs. When a CTL's CD8 receptor docks to a MHC class I molecule, if the CTL's TCR fits the epitope within the MHC class I molecule, the CTL triggers the cell to undergo programmed cell death by apoptosis. Thus, MHC class I helps mediate cellular immunity, a primary means to address intracellular pathogens, such as viruses and some bacteria, including bacterial L forms, bacterial genus "Mycoplasma", and bacterial genus "Rickettsia". In humans, MHC class I comprises HLA-A, HLA-B, and HLA-C molecules. MHC

neg: MHC class I to the MHC molecule and serves to link it to the TAP proteins, thus facilitating enhanced peptide loading and colocalization. Once the peptide is loaded onto the MHC class I molecule, the complex dissociates and it leaves the ER through the secretory pathway to reach the cell surface. The transport of the MHC class I molecules through the secretory pathway involves several posttranslational modifications of the MHC molecule. Some of the posttranslational modifications occur in the ER and involve change to the N-glycan regions of the protein, followed by extensive changes to the N-glycans in the Golgi apparatus. The N-glycans

neg: CD94/NKG2 (C-lectin related) genes. NKG2 receptors are transmembrane proteins type II which dimerize with CD94 molecule. CD94 contains a short cytoplasmic domain and it is responsible for signal transduction. Therefore NKG2 receptors form disulfide bonded heterodimers. NKG2D represent an exception, it is a homodimer. Receptors of CD94/NKG2 family bind nonclassical MHC glycoproteins class I (HLA-E in human and Qa-1 molecules in the mouse). Nonclassical MHC glycoproteins class I are structurally similar to classical MHC class I molecules, but they present mainly peptides derived from the signal peptides of MHC class I. Therefore NK cells can indirectly monitor the expression of classical

neg: MHC class I polypeptide-related sequence A regulated by promoter heat shock element. MICA is broadly recognized by NK cells, γδ T cells, and CD8 αβ T cells which carry NKG2D receptor on their cell surface. As a result of NKG2D-MICA engagement, effector cytolytic responses of T cells and NK cells against epithelial tumor cells expressing MICA are initiated. MHC class I polypeptide-related sequence A MHC class I polypeptide-related sequence A (MICA) is a cell surface glycoprotein encoded by the "MICA" gene located within MHC locus. MICA is related to MHC class I and has similar domain structure, which is made up of external α1α2α3 domain, transmembrane

neg: Tumor antigens recognized by T lymphocytes Tumor antigens recognized by T lymphocytes T lymphocytes are cells of the immune system that attack and destroy virus-infected cells, tumor cells and cells from transplanted organs. This occurs because each T cell is endowed with a highly specific receptor that can bind to an antigen present at the surface of another cell. The T cell receptor binds to a complex formed by a surface protein named "MHC" (major histocompatibility complex) and a small peptide of about 9 amino-acids, which is located in a groove of the MHC molecule. This peptide can originate from a protein that remains within the

neg: Tumor antigens recognized by T lymphocytes protein. This can result in the presentation of a new peptide by an MHC molecule. In some instances, the normal sequence does not enable the peptide to bind to a MHC molecule whereas the new peptide does. Hence, a new antigen is present only on the tumor cells. In other instances, the normal peptide is presented at the cell surface and consequently the T lymphocytes that recognize the antigen have been eliminated by the central tolerance process that occurs in the thymus. The mutated peptide is recognized by other T cells which have not been eliminated by central tolerance because

neg: Cross-presentation antigen by a dendritic cell. Endocytosis results in the formation of a phagocytic vesicle, where an increasingly acidic environment along with the activation of enzymes such as lysosomal proteases triggers the degradation of antigen into peptides. The peptides can then be loaded onto MHC I binding grooves within the phagosome. It is unclear whether the MHC I molecule is being exported from the endoplasmic reticulum before peptide loading, or is being recycled from the cell membrane prior to peptide loading. Once the exogenous antigen peptide is loaded onto the MHC class I molecule, the complex is exported to the cell

neg: HLA-E been shown to trigger expansion of NK cell subsets in antiviral responses. HLA-E HLA class I histocompatibility antigen, alpha chain E (HLA-E) also known as MHC class I antigen E is a protein that in humans is encoded by the "HLA-E" gene. The human HLA-E is a non-classical MHC class I molecule that is characterized by a limited polymorphism and a lower cell surface expression than its classical paralogues. The functional homolog in mice is called Qa-1b, officially known as H2-T23. Like other MHC class I molecules, HLA-E is a heterodimer consisting of an α heavy chain and a light

neg: Major histocompatibility complex epitope coupled within the MHC class II. This event primes the naive helper T cell. According to the local milieu, that is, the balance of cytokines secreted by APCs in the microenvironment, the naive helper T cell (Th) polarizes into either a memory Th cell or an effector Th cell of phenotype either type 1 (Th), type 2 (Th), type 17 (Th), or regulatory/suppressor (T), as so far identified, the Th cell's terminal differentiation. MHC class II thus mediates immunization to—or, if APCs polarize Th cells principally to T cells, immune tolerance of—an antigen. The polarization during primary exposure to

neg: T-cell receptor naive T cell. The signal from the T-cell complex is enhanced by simultaneous binding of the MHC molecules by a specific co-receptor. Extracellularly, the TCR co-receptor defines the specificity of the TCR to MHC class I or II molecule, and increases binding affinity of TCR to MHC to prolong the cell-cell interaction between the antigen-presenting cell and the T cell. Intracellularly, the TCR co-receptor recruits essential molecules (e.g., LCK) involved in the signaling of the activated T lymphocyte to facilitate the CD3 signal transduction mechanism. The essential function of the TCR complex is to identify specific bound antigen and elicit

neg: Plasma cell cell acts as an antigen presenting cell (APC) and internalizes offending antigens, which are taken up by the B cell through receptor-mediated endocytosis and processed. Pieces of the antigen (which are now known as "antigenic peptides") are loaded onto MHC II molecules, and presented on its extracellular surface to CD4+ T cells (sometimes called "T helper cells"). These T cells bind to the MHC II-antigen molecule and cause activation of the B cell. This is a type of safeguard to the system, almost like a two-factor authentication method. First, the B cells have to encounter a foreign antigen, and are

neg: Major histocompatibility complex molecule to the cell membrane. The peptide being presented is held by the floor of the peptide-binding groove, in the central region of the α1/α2 heterodimer (a molecule composed of two nonidentical subunits). The genetically encoded and expressed sequence of amino acids, the sequence of residues, of the peptide-binding groove's floor determines which particular peptide residues it binds. Classical MHC molecules present epitopes to the TCRs of CD8+ T lymphocytes. Nonclassical molecules (MHC class IB) exhibit limited polymorphism, expression patterns, and presented antigens; this group is subdivided into a group encoded within MHC loci (e.g., HLA-E, -F, -G), as well

neg: Hugh McDevitt of antigen recognition and induction of the immune response." His research focuses on identifying and understanding how certain cells and specific sequence polymorphisms in a class II MHC molecule initiate diabetes and how T cells can prevent and suppress the transfer of diabetes. Along with Dr. Qing Li, they discovered that interferon-alpha, and immune signal, can trigger the onset of type-1 diabetes. "A normal process - programmed cell death - causes a normal response," McDevitt said. "But it does this in such a way that, in a small subset of the population, it starts them on the road to type-1

neg: Mucosal associated invariant T cell phenotype in the periphery, mature MAIT cells express a CD44, CD45RO, CCR7, CD62L phenotype. Like all T cell subsets, MAIT cells develop in the thymus. Here, T cells rearrange their TCRs and are subjected to TCR affinity tests as a part of positive selection and negative selection. However, rather than undergoing selection on MHC class I or II molecules, MAIT cells interact with the MHC class I-like molecule, MR1, on thymocytes. MR1 also serves as the antigen-presenting molecule outside of the thymus that binds to TCR and activates MAIT cells. MAIT cells display effector-like qualities before leaving the thymus, which

neg: Human leukocyte antigen recognize foreign antigens — a requirement known as MHC restriction. These cells have receptors that are similar to B cell receptors, and each cell recognizes only a few class II-peptide combinations. Once a T cell recognizes a peptide within an MHC class II molecule, it can stimulate B-cells that also recognize the same molecule in their B cell receptors. Thus, T cells help B cells make antibodies to the same foreign antigens. Each HLA can bind many peptides, and each person has 3 HLA types and can have 4 isoforms of DP, 4 isoforms of DQ and 4 Isoforms of

neg: MHC class II cell surface. In humans, the MHC class II protein complex is encoded by the human leukocyte antigen gene complex (HLA). HLAs corresponding to MHC class II are HLA-DP, HLA-DM, HLA-DOA, HLA-DOB, HLA-DQ, and HLA-DR. Mutations in the HLA gene complex can lead to bare lymphocyte syndrome (BLS), which is a type of MHC class II deficiency. Like MHC class I molecules, class II molecules are also heterodimers, but in this case consist of two homogenous peptides, an α and β chain, both of which are encoded in the MHC. The subdesignation α1, α2, etc. refers to separate domains within the

neg: MHC restriction cell maturation during selection. The TCRs of T cells recognize linear peptide antigens only if coupled with a MHC molecule. In other words, the ligands of TCRs are specific peptide-MHC complexes. MHC restriction is particularly important for self-tolerance, which makes sure that our immune system do not target ourselves. When primary lymphocytes are developing and differentiating in the thymus or bone marrow, T cells die by apoptosis if they express high affinity for self-antigens presented by an MHC molecule or express too low an affinity for self MHC. T cell maturation involves two distinct developmental stages: positive selection and negative

neg: Major histocompatibility complex peptide-binding groove of the MHC molecule interacts with the variable Ig-Like domain of the TCR to trigger T-cell activation Autoimmune reaction: Having some MHC molecules increases the risk of autoimmune diseases more than having others. HLA-B27 is an example. It is unclear how exactly having the HLA-B27 tissue type increases the risk of ankylosing spondylitis and other associated inflammatory diseases, but mechanisms involving aberrant antigen presentation or T cell activation have been hypothesized. Tissue allorecognition: MHC molecules in complex with peptide epitopes are essentially ligands for TCR. T cells become activated by binding to the peptide-binding grooves of any MHC

neg: Cross-presentation for loading onto MHC class I complexes. It is believed that MHC I loading occurs both in the ER as well as phagocytic vesicles such as an endosome in the cytosolic pathway. For MHC class I loading within the Endoplasmic Reticulum, exogenous antigen peptides are loaded onto MHC class I molecules with the help of the peptide loading complex and chaperone proteins such as beta-2 microglobulin, ERAP, tapapsin, and calreticulin. After antigen peptide loading, the MHC molecule is transported out of the ER, through the Golgi complex, and then onto the cell surface for cross presentation. It appears that both

neg: CLIP (protein) II molecule, releasing CLIP and allowing peptides to bind. MHC II with bound antigen is then transported to the cell membrane for presentation. HLA-DO can inhibit the reaction catalysed by HLA-DM. CLIP plays a role in myeloid leukemia. CLIP (protein) CLIP or Class II-associated invariant chain peptide is the part of the invariant chain (Ii) that binds MHC class II groove and remains there until the MHC receptor is fully assembled. The purpose of CLIP is to prevent the binding of self-peptide fragments prior to MHC II localization within the endo/lysosome. During MHC II assembly, invariant chain complexes with the

neg: Killer-cell immunoglobulin-like receptor similar Lirilumab is intended for the treatment of cancers e.g. leukemia. Killer-cell immunoglobulin-like receptor Killer-cell immunoglobulin-like receptors (KIRs), are a family of type I transmembrane glycoproteins expressed on the plasma membrane of natural killer (NK) cells and a minority of T cells. They regulate the killing function of these cells by interacting with major histocompatibility (MHC) class I molecules, which are expressed on all nucleated cell types. KIR receptors can distinguish between major histocompatibility (MHC) class I allelic variants, which allows them to detect virally infected cells or transformed cells. Most KIRs are inhibitory, meaning that their recognition of MHC

neg: Toxic shock syndrome TSS (caused by "S. aureus") and TSLS (caused by "S. pyogenes"), disease progression stems from a superantigen toxin that allows the nonspecific binding of MHC II with T-cell receptors, resulting in polyclonal T-cell activation. In typical T-cell recognition, an antigen is taken up by an antigen-presenting cell, processed, expressed on the cell surface in complex with class II major histocompatibility complex (MHC) in a groove formed by the alpha and beta chains of class II MHC, and recognized by an antigen-specific T-cell receptor. By contrast, superantigens do not require processing by antigen-presenting cells but instead interact directly with the invariant

neg: CD8 initiates a cascade of phosphorylation eventually leading to activation of transcription factors like NFAT, NF-κB, and AP-1 which affect the expression of certain genes. CD8 CD8 (cluster of differentiation 8) is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor (TCR). Like the TCR, CD8 binds to a major histocompatibility complex (MHC) molecule, but is specific for the class I MHC protein. There are two isoforms of the protein, alpha and beta, each encoded by a different gene. In humans, both genes are located on chromosome 2 in position 2p12. The CD8 co-receptor is predominantly expressed

neg: Lymphocyte a major role in defending the host from tumors and virally infected cells. NK cells distinguish infected cells and tumors from normal and uninfected cells by recognizing changes of a surface molecule called MHC (major histocompatibility complex) class I. NK cells are activated in response to a family of cytokines called interferons. Activated NK cells release cytotoxic (cell-killing) granules which then destroy the altered cells. They are named "natural killer cells" because they do not require prior activation in order to kill cells which are missing MHC class I. Mammalian stem cells differentiate into several kinds of blood cell within

neg: HLA-E HLA-E HLA class I histocompatibility antigen, alpha chain E (HLA-E) also known as MHC class I antigen E is a protein that in humans is encoded by the "HLA-E" gene. The human HLA-E is a non-classical MHC class I molecule that is characterized by a limited polymorphism and a lower cell surface expression than its classical paralogues. The functional homolog in mice is called Qa-1b, officially known as H2-T23. Like other MHC class I molecules, HLA-E is a heterodimer consisting of an α heavy chain and a light chain (β-2 microglobulin). The heavy chain is approximately 45 kDa and anchored

neg: Antigen presentation and sometimes also endogenous ones, are enclosed into endocytic vesicles and presented on the cell surface by MHC-II molecules to the helper T cells expressing CD4 molecule. Only APCs do express the class II of MHC molecules on the surface in large quantity, such as dendritic cells, B cells or macrophages, so expression of MHC-II molecules is more cell-specific than MHC-I. APCs usually internalise exogenous antigens by endocytosis, but also by pinocytosis, macroautophagy, endosomal microautophagy or chaperone-mediated autophagy. In the first case, after internalisation, the antigens are enclosed in vesicles called endosomes. There are three compartements involved in this antigen

neg: Superantigen the enterotoxins reveals that they are compact, ellipsoidal proteins sharing a characteristic two-domain folding pattern comprising an NH2-terminal β barrel globular domain known as the oligosaccharide / oligonucleotide fold, a long α-helix that diagonally spans the center of the molecule, and a COOH terminal globular domain. The domains have binding regions for the Major Histocompatibility Complex Class II (MHC Class II) and the T cell receptor (TCR), respectively. Superantigens bind first to the MHC Class II and then coordinate to the variable alpha or beta chain of T-cell Receptors (TCR) SAgs show preference for the HLA-DQ form of the molecule.

neg: Autoimmunity MHC Class II molecule (H-2) to temporarily prevent CD4+ T cell-MHC interaction. Naive CD4+ T cells (those that have not encountered any antigens before) recovered from these mice 36 hours post-anti-MHC administration showed decreased responsiveness to the antigen pigeon cytochrome C peptide, as determined by Zap-70 phosphorylation, proliferation, and Interleukin-2 production. Thus Stefanova et al. (2002) demonstrated that self-MHC recognition (which, if too strong may contribute to autoimmune disease) maintains the responsiveness of CD4+ T cells when foreign antigens are absent. This idea of autoimmunity is conceptually similar to play-fighting. The play-fighting of young cubs (TCR and self-MHC) may result

neg: MHC class I mature fully before they reach the cell surface. Peptides that fail to bind MHC class I molecules in the lumen of the endoplasmic reticulum (ER) are removed from the ER via the sec61 channel into the cytosol, where they might undergo further trimming in size, and might be translocated by TAP back into ER for binding to an MHC class I molecule. For example, an interaction of sec61 with bovine albumin has been observed. MHC class I molecules are loaded with peptides generated from the degradation of ubiquitinated cytosolic proteins in proteasomes. As viruses induce cellular expression of viral proteins,

neg: Killer-cell immunoglobulin-like receptor Killer-cell immunoglobulin-like receptor Killer-cell immunoglobulin-like receptors (KIRs), are a family of type I transmembrane glycoproteins expressed on the plasma membrane of natural killer (NK) cells and a minority of T cells. They regulate the killing function of these cells by interacting with major histocompatibility (MHC) class I molecules, which are expressed on all nucleated cell types. KIR receptors can distinguish between major histocompatibility (MHC) class I allelic variants, which allows them to detect virally infected cells or transformed cells. Most KIRs are inhibitory, meaning that their recognition of MHC molecules suppresses the cytotoxic activity of their NK cell. Only a

neg: MHC restriction MHC restriction MHC-restricted antigen recognition, or MHC restriction, refers to the fact that a given T cell can interact with both the self-major histocompatibility complex molecule and the foreign peptide that is bound to it, but will recognize and respond to the antigen, only when it is bound to a particular MHC molecule. When foreign proteins enter a cell, they are broken into smaller pieces called peptides. These peptides, also known as antigens, can derive from pathogens such as viruses or intracellular bacteria. Foreign peptides are brought to the surface of the cell and presented to T cells by proteins

neg: T-cell receptor dimeric signaling modules CD3δ/ε, CD3γ/ε and CD247 ζ/ζ or ζ/η. Ionizable residues in the transmembrane domain of each subunit form a polar network of interactions that hold the complex together. Since the cytoplasmic tail of the TCR is extremely short, making it unlikely to participate in signaling, these signaling molecules are vital in propagating the signal from the triggered TCR into the cell. Each T cell expresses clonal TCRs which recognize specific peptide/MHC complex during physical contact between T cell and antigen-presenting cell-APC (MHC class II) or any other cell type (MHC class I) High on-rate and off-rate is characteristic

neg: T cell with MHC class I molecules, which are present on the surface of all nucleated cells. Through IL-10, adenosine, and other molecules secreted by regulatory T cells, the CD8 cells can be inactivated to an anergic state, which prevents autoimmune diseases. Antigen-naïve T cells expand and differentiate into memory and effector T cells after they encounter their cognate antigen within the context of an MHC molecule on the surface of a professional antigen presenting cell (e.g. a dendritic cell). Appropriate co-stimulation must be present at the time of antigen encounter for this process to occur. Historically, memory T cells were thought

neg: Lipid raft surface, and their participation in antigen presentation to T cells. Viruses, as obligate intracellular parasites, have to involve specific interaction of virus and cellular receptor expressed at the plasma membrane in order to enter cells. Accumulated evidence supports that viruses enter cells via penetration of specific membrane microdomains, including lipid rafts. The best studied models of lipid rafts-related nonenveloped viral entry are simian virus 40 (SV40, Papovaviridae) and echovirus type 1 (EV1, Picornaviridae). SV40 utilizes two different receptors to bind onto cell surface: ganglioside GM1 located in lipid rafts and major histocompatibility (MHC) class I molecule. Binding of SV40 with

neg: MHC class II MHC-II loaded vesicles within the Immature Dendritic Cell, impeding its translocation to the cell membrane. One type of MHC class II deficiency, also called bare lymphocyte syndrome, is due to mutations in the genes that code for transcription factors that regulate the expression of the MHC class II genes. It results in the depletion of CD4 T cells and some immunoglobulin isotypes even though there are normal levels of both CD8 Cells and B cells present. Deficient MHC class II molecules are unable to present antigens to T cells and properly activate T cells. T cells are then unable to

neg: RFXANK RFXANK DNA-binding protein RFXANK is a protein that in humans is encoded by the "RFXANK" gene. Major histocompatibility (MHC) class II molecules are transmembrane proteins that have a central role in development and control of the immune system. The protein encoded by this gene, along with regulatory factor X-associated protein and regulatory factor-5, forms a complex that binds to the X box motif of certain MHC class II gene promoters and activates their transcription. Once bound to the promoter, this complex associates with the non-DNA-binding factor MHC class II transactivator, which controls the cell type specificity and inducibility of MHC

neg: Adaptive immune system in which they lose most of their ability to engulf other pathogens, and develop an ability to communicate with T-cells. The dendritic cell uses enzymes to chop the pathogen into smaller pieces, called antigens. In the lymph node, the dendritic cell displays these non-self antigens on its surface by coupling them to a receptor called the major histocompatibility complex, or MHC (also known in humans as human leukocyte antigen (HLA)). This MHC: antigen complex is recognized by T-cells passing through the lymph node. Exogenous antigens are usually displayed on MHC class II molecules, which activate CD4+T helper cells. Endogenous antigens

neg: T-cell receptor which then attracts PLC-γ. Other downstream pathways are triggered as well (MAPK, NF-κB, NFAT) which results in gene transcription in the nucleus. T-cell receptor The T-cell receptor, or TCR, is a molecule found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The binding between TCR and antigen peptides is of relatively low affinity and is degenerate: that is, many TCRs recognize the same antigen peptide and many antigen peptides are recognized by the same TCR. The TCR is composed of two different

neg: Major histocompatibility complex as those not (e.g., stress ligands such as ULBPs, Rae1, and H60); the antigen/ligand for many of these molecules remain unknown, but they can interact with each of CD8+ T cells, NKT cells, and NK cells. MHC class II is formed of two chains, α and β, each having two domains—α1 and α2 and β1 and β2—each chain having a transmembrane domain, α2 and β2, respectively, anchoring the MHC class II molecule to the cell membrane. The peptide-binding groove is formed of the heterodimer of α1 and β1. MHC class II molecules in humans have five to six isotypes. Classic

neg: Antigen-presenting cell an MHC class I molecule. Non-professional APCs do not typically express MHC class II molecules. However, it has been observed that antigen presentation to CD4+ cells via MHC class II is not restricted to the classically professional APCs. Other leukocytes, including granulocytes such as mast cells and neutrophils, can be induced to do so, as can endothelial and epithelial cells under certain circumstances. Even so, there is little evidence that these atypical APCs are able to activate naive CD4+ T cells. After dendritic cells have phagocytosed pathogens, they usually migrate to the vast network of lymph vessels and are carried

neg: Minor histocompatibility antigen graft-versus- leukemia effect (GVL). The recognition of a mature T cell to this self antigen should not induce an immune response. During thymic selection occurring in the thymus, only a thymocyte TCR that recognizes either class I or class II MHC molecule plus peptide should survive positive selection. However, there is death by apoptosis of thymocytes that do not interact with MHC molecules or have high-affinity receptors for self MHC plus self antigen a process referred to as negative selection. Therefore, the process of positive and negative selection means fewer self-reactive mature T cells will leave the thymus and lead

neg: T helper cell the lymph nodes. Once at the lymph nodes, the APCs begin to present antigen peptides that are bound to Class II MHC, allowing CD4 T cells that express the specific TCRs against the peptide/MHC complex to activate. When a T cell encounters and recognises the antigen on an APC, the TCR-CD3 complex binds strongly to the peptide-MHC complex present on the surface of professional APCs. CD4, a co-receptor of the TCR complex, also binds to a different section of the MHC molecule. These interactions bring these proteins closer together, allowing the intracellular kinases present on the TCR, CD3 and CD4

neg: Tetrameric protein receptors that are specific for a given peptide-MHC complex. For example, a Kb/FAPGNYPAL tetramer will specifically bind to Sendai virus specific cytotoxic T cell in a C57BL/6 mouse. Antigen specific responses can be measured as CD8+, tetramer+ T cells as a fraction of all CD8+ lymphocytes. The reason for using a tetramer, as opposed to a single labeled MHC class I molecule is that the tetrahedral tetramers can bind to three TCRs at once, allowing specific binding in spite of the low (10-6 molar) affinity of the typical class I-peptide-TCR interaction. MHC class II tetramers can also be made although

neg: ULBP1 of HCMV-encoded UL16 glycoprotein to ULBP1 interferes with cell surface localization of ULBP1; this represents another mechanism by which HCMV-infected cells might escape the immune system. ULBP1 UL16 binding protein 1 (ULBP1) is a cell surface glycoprotein encoded by "ULBP1" gene located on the chromosome 6. ULBP1 is related to MHC class I molecules, but its gene maps outside the MHC locus. The domain structure of ULBP1 differs significantly from those of conventional MHC class I molecules. It does not contain the α3 domain and the transmembrane segment. ULBP1 is thus composed of only the α1α2 domain which is linked

neg: CGAS–STING cytosolic DNA sensing pathway STING remains to be determined. The signaling pathways activated by STING combine to induce an innate immune response to cells with ectopic DNA in the cytosol. Loss of STING activity inhibits the ability of mouse embryonic fibroblasts to fight against infection by certain viruses, and more generally, is required for the type 1 IFN response to introduced cytosolic DNA. STING’s general role as an adapter molecule in the cytosolic DNA-type 1 IFN response across cell types has been suggested to function through dendritic cells (DCs). DCs link the innate immune system with the adaptive immune system through phagocytosis and MHC

neg: Mixed lymphocyte reaction to external stimuli. T cells are a type of white blood cell that scans for cellular abnormalities and infections. They are essential to human immunity. The MLR was first recognized when researchers mixed leukocytes from two unrelated donors in culture. After several days, lymphocytes underwent blast transformation, DNA synthesis and cellular proliferation in response to the major histocompatibility antigen (MHC Class I and II) differences between the two cell populations designated as Responder and Stimulator cells. Responder cells proliferated without previous exposure to Stimulator MHC antigens. This response became quantifiable when incorporating radioactivity, [3H] thymidine or 5-bromo-2’-deoxyuridine (BrdU), into the

neg: MHC class I cytoplasmic side and translocates them under ATP consumption into the lumen of the ER. The MHC class I molecule is then, in turn, loaded with peptides in the lumen of the ER. The peptide-loading process involves several other molecules that form a large multimeric complex consisting of TAP, tapasin, calreticulin, calnexin, and Erp57 (PDIA3). Calnexin acts to stabilize the class I MHC α chains prior to β2m binding. Following complete assembly of the MHC molecule, calnexin dissociates. The MHC molecule lacking a bound peptide is inherently unstable and requires the binding of the chaperones calreticulin and Erp57. Additionally, tapasin binds

neg: ULBP1 ULBP1 UL16 binding protein 1 (ULBP1) is a cell surface glycoprotein encoded by "ULBP1" gene located on the chromosome 6. ULBP1 is related to MHC class I molecules, but its gene maps outside the MHC locus. The domain structure of ULBP1 differs significantly from those of conventional MHC class I molecules. It does not contain the α3 domain and the transmembrane segment. ULBP1 is thus composed of only the α1α2 domain which is linked to the cell membrane by the GPI anchor. It functions as a stress-induced ligand for NKG2D receptor. ULBP1 is, for example, upregulated during HCMV infection. Binding

neg: MHC restriction during positive selection in the thymus, to some extent evolutionary pressure selects for germline TCR sequences that bind MHC molecules. On the other hand, as suggested by the selection model, T cell maturation requires the TCRs to bind to the same MHC molecules as the CD4 or CD8 co-receptor during T cell selection, thus imposing MHC restriction. MHC restriction MHC-restricted antigen recognition, or MHC restriction, refers to the fact that a given T cell can interact with both the self-major histocompatibility complex molecule and the foreign peptide that is bound to it, but will recognize and respond to the antigen,

neg: HLA-A HLA-A HLA-A is a group of human leukocyte antigens (HLA) that are coded for by the HLA-A locus, which is located at human chromosome 6p21.3. HLA is a major histocompatibility complex (MHC) antigen specific to humans. HLA-A is one of three major types of human MHC class I cell surface receptors. The others are HLA-B and HLA-C. The receptor is a heterodimer, and is composed of a heavy α chain and smaller β chain. The α chain is encoded by a variant HLA-A gene, and the β chain (β-microglobulin) is an invariant β microglobulin molecule. The β microglobulin protein is

neg: Enterotoxin type B II molecules with T-cell receptors. TSST is a multisystem illness with several symptoms such as high fever, hypotension, dizziness, rash and peeling skin. All of these toxins share a similar two-domain fold (N and C-terminal domains) with a long alpha-helix in the middle of the molecule, a characteristic beta-barrel known as the "oligosaccharide/oligonucleotide fold" at the N-terminal domain and a beta-grasp motif at the C-terminal domain. Each superantigen possesses slightly different binding mode(s) when it interacts with MHC class II molecules or the T-cell receptor. The N-terminal domain is also referred to as OB-fold, or in other words the oligonuclucleotide

neg: SCIMP protein is associated with tetraspanin-enriched mircrodomains (TEMs). TEMs, unlike lipid rafts, are based more on protein-protein interactions than lipid-lipid/lipid-protein interactions. One of the resident proteins in TEMs is MHC class II molecule. SCIMP is present in the immunological synapse during antigen presentation between a T cell and an antigen-presenting cell (APC). SCIMP becomes strongly phosphorylated after MHC II stimulation. Studies performed with fusion protein CD25-SCIMP showed its ability to induce calcium release and Erk phosphorylation upon anti-CD25 antibody treatment. The calcium release was even stronger in CD25-SCIMP mutant protein in binding side for Csk. Indicating negative feedback loop performed by Csk

neg: HLA-DQ to be increased in Heterozygotes are Celiac Disease and Type 1 Diabetes. New evidence is showing an increased risk for late onset Type 1 diabetes in Heterozygotes (which includes ambiguous Type I/Type II diabetes). 95% of Celiac Disease patients are positive for DQ2 or DQ8. HLA-DQ HLA-DQ (DQ) is a cell surface receptor protein found on antigen presenting cells. It is an αβ heterodimer of type MHC class II. The α and β chains are encoded by two loci, HLA-DQA1 and HLA-DQB1, that are adjacent to each other on chromosome band 6p21.3. Both α-chain and β-chain vary greatly. A person

neg: Plasmacytoid dendritic cell bone marrow as precursors, pDCs leave the bone marrow to go to the lymphoid organs and peripheral blood upon completing development. Plasmacytoid dendritic cells are also distinguished from cDCs because of their ability to produce significant amounts of type-1 interferon. pDC maturation is initiated when the cell comes in contact with a virus, prompting the upregulation of MHC class I and MHC class II, co-stimulatory molecules CD80, CD86, CD83, and c-c chemokine receptor 7 (CCR7) and interferon production gradually decreases. CCR7 expression prompts the matured pDC to migrate to a lymph node where it will be able to stimulate and

neg: Immune system cells, each type of T cell recognizes a different antigen. Killer T cells are activated when their T-cell receptor (TCR) binds to this specific antigen in a complex with the MHC Class I receptor of another cell. Recognition of this MHC:antigen complex is aided by a co-receptor on the T cell, called CD8. The T cell then travels throughout the body in search of cells where the MHC I receptors bear this antigen. When an activated T cell contacts such cells, it releases cytotoxins, such as perforin, which form pores in the target cell's plasma membrane, allowing ions, water and

neg: Vincenzo Cerundolo relationship between the length of peptides and their binding affinity to MHC class I molecules, explaining the homogeneous length of peptides isolated from MHC class I molecules. He characterised the structural and kinetic mechanisms by which lipids bind to CD1 molecules and are recognized by T cells and demonstrated that harnessing CD1 restricted Natural killer T cell (NKT) cells enhances antigen specific antibody and T cell responses. Enzo became Director of the MRC Human Immunology Unit in 2010 and has supervised over 35 DPhil students and postdoctoral fellows, many of whom have gone to become leading immunologists themselves: In 1987

neg: Tapasin Tapasin TAP-associated glycoprotein also known as tapasin or TAPBP is a protein that in humans is encoded by the "TAPBP" gene. This gene encodes a transmembrane glycoprotein that mediates interaction between newly assembled major histocompatibility complex (MHC) class I molecules and the transporter associated with antigen processing (TAP), which is required for the transport of antigenic peptides across the endoplasmic reticulum membrane. This interaction facilitates optimal peptide loading on the MHC class I molecule. Up to four complexes of MHC class I and tapasin may be bound to a single TAP molecule. Tapasin contains a C-terminal double-lysine motif (KKKAE) known

neg: Cortical thymic epithelial cells their transformation from double negative stages (T cell without surface expression of CD4 and CD8 co-receptors) to a double positive stage (T cell with surface expression of both co-receptors) that expresses fully recombined TCR. This stage undergoes above mentioned selection process. Interaction between TCR of double positive T cell and MHC I molecule leads to loss of CD4 expression and double positive T cell becomes CD8 single positive T cell, conversely, engagement of MHC II molecule leads to the development into CD4 single positive T cell. It was also described that CD8/CD4 restriction is influenced by transcription factors Runx3, in

neg: Killer-cell immunoglobulin-like receptor are each expressed on a subset of NK cells in such a way that not all classes of inhibitory NK cell receptors are expressed on each NK cell, but there is some overlap. This creates unique repertories of NK cells, increasing the specificity with which NK cells recognize virally-infected and transformed self-cells. Expression of KIR receptors is determined primarily by genetic factors, but recent studies have found that epigenetic mechanisms also play a role in KIR receptor expression. Activating and inhibitory KIR receptors that recognize the same class I MHC molecule are mostly not expressed by the same NK cell.

neg: Macrophage pursuit of microbes and tumour cells. After digesting a pathogen, a macrophage will present the antigen (a molecule, most often a protein found on the surface of the pathogen and used by the immune system for identification) of the pathogen to the corresponding helper T cell. The presentation is done by integrating it into the cell membrane and displaying it attached to an MHC class II molecule (MHCII), indicating to other white blood cells that the macrophage is not a pathogen, despite having antigens on its surface. Eventually, the antigen presentation results in the production of antibodies that attach to

neg: HLA-DM In order to ensure that no false peptides bind to an MHC class II molecule, the peptide-binding groove is occupied by a protein called CLIP. Once a proper peptide is encountered, HLA-DM catalyzes the exchange of CLIP for an antigen peptide. Often, this peptide is retrieved directly from the B cell receptor which internalized it. Through expulsion of CLIP at the proper time, HLA-DM ensures that the correct antigen can bind to MHC molecules and prevent either from degrading. Apart from CLIP-antigen exchange, HLA-DM also facilitates antigen-antigen exchange. It releases weakly bound peptides from the groove to load peptides with

neg: Polyclonal B cell response type of white blood cell. This is known as "antigen presentation." However, the epitopes (conformational epitopes) that are recognized by the B cell prior to their digestion may not be the same as that presented to the T helper cell. Additionally, a B cell may present different peptides complexed to different MHC-II molecules. The CD 4+ cells through their T cell receptor-CD3 complex recognize the epitope-bound MHC II molecules on the surface of the antigen presenting cells, and get 'activated'. Upon this activation, these T cells proliferate and differentiate into T2 cells. This makes them produce soluble chemical signals that

neg: Toxic shock syndrome region of the class II MHC molecule. In patients with TSS, up to 20% of the body's T-cells can be activated at one time. This polyclonal T-cell population causes a cytokine storm, followed by a multisystem disease. The toxin in "S. aureus" infections is TSS Toxin-1, or TSST-1. The TSST-1 is secreted as a single polypeptide chain. The gene encoding toxic shock syndrome toxin is carried by a mobile genetic element of "S. aureus" in the SaPI family of pathogenicity islands. For staphylococcal toxic shock syndrome, the diagnosis is based upon CDC criteria defined in 2011, as follows: Cases are

neg: C-C chemokine receptor type 7 various lymphoid tissues and activates B and T lymphocytes. CCR7 has been shown to stimulate dendritic cell maturation. CCR7 is also involved in homing of T cells to various secondary lymphoid organs such as lymph nodes and the spleen as well as trafficking of T cells within the spleen. Activation of Dendritic cells in peripheral tissues induces CCR7 expression on the cell's surface, which recognize CCL19 and CCL21 produced in the Lymph node and increases dendritic cell expression of co-stimulation molecules (B7), and MHC class I or MHC class II. CCR7 is expressed by various cancer cells, such as nonsmall

neg: Human leukocyte antigen class I) on the cell surface. Infected cells can be recognized and destroyed by CD8+ T cells. The image off to the side shows a piece of a poisonous bacterial protein (SEI peptide) bound within the binding cleft portion of the HLA-DR1 molecule. In the illustration far below, a different view, one can see an entire DQ with a bound peptide in a similar cleft, as viewed from the side. Disease-related peptides fit into these "slots" much like a hand fits into a glove. When bound, peptides are presented to T cells. T cells require presentation via MHC molecules to

neg: Peripheral tolerance an MHC molecule on an antigen presenting cell (signal 1) without engagement of costimulatory molecules (signal 2). Co-stimulatory molecules are upregulated by cytokines in the context of acute inflammation. Without pro-inflammatory cytokines, co-stimulatory molecules will not be expressed on the surface of the antigen presenting cell, and so anergy will result if there is an MHC-TCR interaction between the T cell and the APC. Since many pathways of immunity are interdependent, they do not all need to be tolerised. For example, tolerised T cells will not activate autoreactive B cells. Without this help from CD4 T cells, the B cells

neg: CD155 select MHC-independent T cells in the thymus. The external domain mediates cell attachment to the extracellular matrix molecule vitronectin, while its intracellular domain interacts with the dynein light chain Tctex-1/DYNLT1. The gene is specific to the primate lineage, and serves as a cellular receptor for poliovirus in the first step of poliovirus replication. CD155 is a transmembrane protein with 3 extracellular immunoglobulin-like domains, D1-D3, where D1 is recognized by the virus. Low resolution structures of CD155 complexed with poliovirus have been obtained using electron microscopy while a high resolution structures of the ectodomain D1 and D2 of CD155 were solved

neg: CD94/NKG2 MHC class I molecules through the interaction of CD94/NKG2 with HLA-E (Qa-1) and HLA-E (Qa-1) themselves as well. NKG2D constitutes an exception. Besides the fact that it is a homodimer, it associates with adaptor molecule DAP10 and its amino acid sequence is identical in only 28% in comparison with other CD94/NKG2 family members, NKG2D binds MHC class I homologues MICA (MHC class I polypeptide-related sequence A), MICB and ULBP (UL-16 binding protein) in human. MICA and MICB are expressed on the surface of epithelial and endothelial cells. The expression of these NKG2D ligands is higher in case of cellular stress,

neg: Tetrameric protein gel filtration experiments and enzyme kinetics experiments, could reveal an important hydrogen bonding network which stabilizes the tetrameric quaternary structure in mammalian SDH. In immunology, MHC tetramers can be used in tetramer assays, to quantify numbers of antigen-specific T cells (especially CD8+ T cells). MHC tetramers are based on recombinant class I molecules that, through the action of bacterial BirA, have been biotinylated. These molecules are folded with the peptide of interest and β2M and tetramerized by a fluorescently labeled streptavidin. (Streptavidin binds to four biotins per molecule.) This tetramer reagent will specifically label T cells that express T cell

neg: T-cell receptor T-cell receptor The T-cell receptor, or TCR, is a molecule found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The binding between TCR and antigen peptides is of relatively low affinity and is degenerate: that is, many TCRs recognize the same antigen peptide and many antigen peptides are recognized by the same TCR. The TCR is composed of two different protein chains (that is, it is a heterodimer). In humans, in 95% of T cells the TCR consists of an alpha (α)

neg: Alloantigen recognition T cell response. Presentation may occur via MHC class I or MHC class II, although class II is usually involved. The main difference between indirect and direct alloantigen recognition stems from the origin of the macrophages (type of APC). In direct alloantigen recognition, the involved dendritic cells are donor derived. In indirect alloantigen recognition, the dendritic cells (APCs) involved are recipient APCs. Alloantigen recognition Alloantigen recognition is the mechanism by which T cells may recognize alloantigens and lead to transplant rejection after an organ transplant. Is is broadly divided into direct and indirect alloantigen recognition. Donor tissue dendritic cells migrate

neg: MHC multimer MHC multimer MHC multimers are oligomeric forms of MHC molecules, designed to identify and isolate T-cells with high affinity to specific antigens amid a large group of unrelated T-cells. Multimers generally range in size from dimers to octamers; however, some companies use even higher quantities of MHC per multimer. Multimers may be used to display class 1 MHC, class 2 MHC, or nonclassical molecules (e.g. CD1d) from species such as monkeys, mice, and humans. Since T-cell receptors have a low affinity for their MHC counterparts, it was historically problematic to label T cells effectively using single MHC-T-cell interactions. However, in

neg: Thymocyte Thymocytes which pass β-selection express a T cell receptor which is capable of assembling on the surface. However, many of these T cell receptors will still be non-functional, due to an inability to bind MHC. The next major stage of thymocyte development is positive selection, to keep only those thymocytes which have a T cell receptor capable of binding MHC. The T cell receptor requires CD8 as a coreceptor to bind to MHC class I, and CD4 as a coreceptor to bind MHC class II. At this stage thymocytes upregulate both CD4 and CD8, becoming double positive cells. Double positive

neg: Polyclonal B cell response segments, called epitopes, can be recognized. An epitope comes in contact with a very small region (of 15–22 amino acids) of the antibody molecule; this region is known as the paratope. In the immune system, membrane-bound antibodies are the B cell receptor (BCR). Also, while the T cell receptor is not biochemically classified as an antibody, it serves a similar function in that it specifically binds to epitopes complexed with major histocompatibility complex (MHC) molecules. The binding between a paratope and its corresponding antigen is very specific, owing to its structure, and is guided by various noncovalent bonds, not unlike

neg: Abatacept as well. In order for T cells to be activated and attack an antigen, that antigen must be presented to the T cell by an antigen-presenting cell (APC). That activation requires two signals (one of which is called co-stimulatory signal or signal 2): For signal 1, the APC must bind the antigen to a major histocompatibility complex (MHC) molecule, bring that complex to its surface, and present it to the T cell receptor on the surface of the T cell. For signal 2, the APC must present a B7 protein on its cell surface to a CD28 protein on the

neg: Thymocyte thymocytes that have a T cell receptor capable of binding MHC class I or class II (even with a weak affinity) receive signalling through the T cell receptor. Thymocytes that have a T cell receptor incapable of binding MHC class I or class II undergo apoptosis. Some thymocytes are able to rescue failed positive selection by receptor editing (rearrangement of the other T cell receptor allele to produce a new T cell receptor). The double positive thymocytes undergo lineage commitment, maturing into a CD8+ T cell (recognising MHC class I) or a CD4+ T cell (recognising MHC class II). Lineage

neg: Antigen presentation as calnexin, clareticulin and tapasin. Peptides are loaded to MHC-I peptide binding groove between two alpha helices at the bottom of the α1 and α2 domains of the MHC class I molecule. After releasing from tapasin, peptide-MHC-I complexes (pMHC-I) exit the ER and are transported to the cell surface by exocytic vesicles. Naïve anti-viral T cells (CD8+) cannot directly eliminate transformed or infected cells. They have to be activated by the pMHC-I complexes of antigen-presenting cells (APCs). Here, antigen can be presented directly (as described above) or indirectly (cross-presentation) from virus-infected and non-infected cells. After the interaction between pMHC-I and

neg: MHC class II MHC class II MHC class II molecules are a class of major histocompatibility complex (MHC) molecules normally found only on antigen-presenting cells such as dendritic cells, mononuclear phagocytes, some endothelial cells, thymic epithelial cells, and B cells. These cells are important in initiating immune responses. The antigens presented by class II peptides are derived from extracellular proteins (not cytosolic as in MHC class I). Loading of a MHC class II molecule occurs by phagocytosis; extracellular proteins are endocytosed, digested in lysosomes, and the resulting epitopic peptide fragments are loaded onto MHC class II molecules prior to their migration to the

neg: Immunogenic cell death cell surface they have an immunostimulatory effect, based on their interaction with number of antigen-presenting cell (APC) surface receptors like CD91 and CD40 and also facilitate crosspresentation of antigens derived from tumour cells on MHC class I molecule, which than leads to the CD8+ T cell response. Other important DAMPs, characteristic for ICD are secreted amphoterin (HMGB1) and ATP. HMGB1 is considered to be late apoptotic marker and its release to the extracellular space seems to be required for the optimal release and presentation of tumour antigens to dendritic cells. It binds to several pattern recognition receptors (PRRs) such as

neg: KLRA1 KLRA1 Ly-49 receptors or killer cell lectin-like receptor subfamily A (KLRA), are a class of natural killer cell receptor. Ly-49 proteins are a diverse set of C-type lectins that are expressed on NK cells in some mammals, including rodents but not humans. Their primary function is to bind host MHC class I as a mechanism of self/health recognition. Upon binding ligands, most Ly-49 receptors will deliver an inhibitory signal, preventing killing of the target cell. In the case of cancer or virally infected cells, MHC-I will often be downregulated in order to limit cytotoxic T cell mediated killing of the

neg: HLA-DM reduced its activity by overexpressing DO found a decrease in diabetes. HLA-DM is implicated in viral infections like "Herpes Simplex Virus Type 1". This virus causes uneven distribution of HLA-DM in endosomes, prevents peptide catalysis, and prevents presentation of MHC class II molecules on the cell surface. HLA-DM is also implicated in celiac disease, multiple sclerosis, other autoimmune diseases, and leukemia. HLA-DM HLA-DM (human leukocyte antigen DM) is an intracellular protein involved in the mechanism of antigen presentation on antigen presenting cells (APCs) of the immune system. It does this by assisting in peptide loading of major histocompatibility complex (MHC)

neg: Killer-cell immunoglobulin-like receptor tyrosine phosphatases, including SHP-1, are recruited. Inhibition occurs early in the activation signaling pathway, likely through the interference of the pathway by these phosphatases. Activating receptors recognize ligands that indicate host cell aberration, including induced-self antigens (which are markers of infected self cells and include MICA, MICB, and ULBP, all of which are related to MHC class 1 molecules), altered-self antigens (MHC class I antigens laden with foreign peptide), and/or non-self (pathogen encoded molecules). The binding of activating KIR receptors to these molecules causes the activation of signaling pathways that cause NK cells to lyse virally infected or transformed cells.

neg: T cell and medulla in the thymus. While in the medulla, they are again presented with a self-antigen presented on the MHC complex of medullary thymic epithelial cells (mTECs). mTECs must be AIRE to properly express self-antigens from all tissues of the body on their MHC class I peptides. Some mTECs are phagocytosed by thymic dendritic cells; this allows for presentation of self-antigens on MHC class II molecules (positively selected CD4 cells must interact with MHC class II molecules, thus APCs, which possess MHC class II, must be present for CD4 T-cell negative selection). Thymocytes that interact too strongly with the self-antigen

neg: Tasmanian devil One strand conformation polymorphism analysis (OSCP) on the major histocompatibility complex (MHC) class I domain taken from various locations across Tasmania showed 25 different types, and showed a different pattern of MHC types in north-western Tasmania to eastern Tasmania. Those devils in the east of the state have less MHC diversity; 30% are of the same type as the tumour (type 1), and 24% are of type A. Seven of every ten devils in the east are of type A, D, G or 1, which are linked to DFTD; whereas only 55% of the western devils fall into these MHC