Whereas MHC class I molecules are expressed on virtually all nucleated cells, MHC class II expression is restricted to professional APCs, such as B cells, dendritic cells and macrophages, and to activated T cells in humans. MHC molecules are membrane glycoproteins that are encoded by several closely linked, highly polymorphic genes. As the αβ TCR does not bind antigen directly, T-cell activation is dependent on an interaction of the TCR with MHC molecules that present small peptide fragments that have been generated from protein antigens. TCR diversity is concentrated in the third hypervariable regions (complementarity determining region 3) of the TCR α and β chains, which form the center of the antigen-binding site of the TCR. Extensive somatic DNA recombination of variable and joining region segments of the α and β TCR genes is responsible for the structural TCR diversity required for reactivity to the huge arsenal of potential antigens. αβ T cells mediate the classical helper or cytotoxic T cell responses. The vast majority of human peripheral blood T cells expresses TCRs consisting of α and β chains (αβ T cells). The cytoplasmic domains of CD4 and CD8 are constitutively associated with the src-family tyrosine kinase p56 lck, which phosphorylates particular recognition motifs within the CD3 complex (denoted immunoreceptor tyrosine-based activation motifs), thereby promoting T-cell activation. Finally, the co-receptors CD4 and CD8, expressions of which are mutually exclusive on mature post-thymic T cells, bind to invariant sites of the MHC class II or I molecules on antigen-presenting cells (APCs), respectively they stabilize the MHC–peptide–TCR complex during T-cell activation, and thus they increase the sensitivity of a T cell for activation by MHC-presented antigen by approximately 100-fold. The TCR–CD3 complex is associated with a largely intracytoplasmic homodimer of ζ-chains that are critical for maximal signaling. The CD3 complex, which consists of four invariant transmembrane polypeptides (designated γδεε) mediates signaling and is also necessary for surface expression of the TCR. The disulfide-linked heterodimeric T-cell receptor (TCR) confers antigen specificity to the T cell. Peripheral T cells are characterized by the expression of an array of distinctive surface receptors. αβ T cells that survive thymic selection lose expression of either CD4 or CD8, increase the level of expression of the TCR, and leave the thymus to form the peripheral T cell repertoire. Whereas αβ T cells are responsible for the classical helper or cytotoxic T cell responses, the function of the γδ T cells within the immune system is largely unknown. αβ and γδ T cells diverge early in T cell development. A small group of peripheral T cells bears an alternative TCR composed of γ and δ chains (γ/δ T cells). In humans, the vast majority of peripheral blood T cells expresses TCRs consisting of α and β chains (αβ T cells). More than 98% of the thymocytes die during maturation by apoptosis (†), as they undergo positive selection for their TCR's compatibility with self-major histocompatibility molecules, and negative selection against those T cells that express TCRs reactive to autoantigenic peptides. Tails of iron igg series#The thymocytes go through a series of maturation steps including distinct changes in the expression of cell surface receptors, such as the CD3 signaling complex (not shown) and the coreceptors CD4 and CD8, and the rearrangement of their antigen receptor ( T cell receptor, TCR) genes. They migrate as immature precursor T cells via the bloodstream into the thymus, which they populate as thymocytes. T cells originate from the common lymphoid progenitor cells in the bone marrow. Schematic representation of T cell development.
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