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All T cells express a receptor for antigen that is formed by two polymorphic polypeptides that invariably are associated with a collection of invariant proteins called CD3γ, CD3δ, CD3ε, and CD247. These invariant proteins are necessary for the surface expression and signaling by the T-cell receptor. The two polypeptides that form the T-cell receptor on most T cells are termed α and β; whereas a small subset of T cells have receptors formed by different polypeptides termed γ and δ. The polypeptides of the T-cell receptor have a diversity that is comparable to that estimated for immunoglobulin molecules. However, unlike immunoglobulins, the T-cell receptors recognize small fragments of antigen, usually peptides, which are nestled in defined peptide-binding groves of major histocompatibility complex molecules that are present on the plasma membrane of another cell. As such, T-cell immune recognition generally requires cognate intercellular interactions between a T cell and another cell, the antigen-presenting cell. The response of the T cell to antigen depends upon the intensity of the signal generated by ligation of the T-cell receptor. In addition, this signal is modified by the simultaneous ligation of other T-cell receptors for accessory molecules on the plasma membrane of the antigen-presenting cell. Because of this, the outcome of T-cell antigen recognition can range from immune activation and T-cell proliferation to specific T-cell tolerance and/or programmed cell death.

Acronyms and Abbreviations

Acronyms and abbreviations that appear in this chapter include: AP-1, activation protein-1 (AP-1); APC, antigen-presenting cell; CTLA-4, cytotoxic T-lymphocyte antigen 4; ERK, extracellular receptor-activated kinase; FoxP3, forkhead box P3; ICAMs, intercellular adhesion molecules; IFN-γ, interferon gamma; IL, interleukin; IPEX syndrome, immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome; ITAMs, immunoreceptor tyrosine-based activation motifs; ITIMs, immunoreceptor tyrosine-based inhibitory motifs; iTreg, induced regulatory T cell; JNK, c-Jun N-terminal kinase; LAT, linker of activation of T cells; LFA, lymphocyte-function-associated; MAP, mitogen-activated protein; MHC, major histocompatibility complex; NFAT, nuclear factor of activated T cells; nTreg, natural regulatory T cell; PKC, protein kinase C; PLC- γ1, phospholipase C-1 gamma; RORγt, retinoic acid-related orphan receptor γ thymus isoform; SAP, stress-activated kinase; SH2 domain, Src homology 2 domain; SH3 domain, Src homology 3 domain; STAT, signal transducer and activator of transcription; Tfh cell, follicular helper T cell; TGF-β, transforming growth factor beta; Th17, CD4+ T-cell subset that produces cytokines of the interleukin-17 family; Treg, CD4+CD25+ regulatory T cells; V-like, variable-region-like; VLA, very-late activation; ZAP-70, zeta-associated protein of 70 kDa.

T-Cell Receptor Heterodimers

The receptor proteins of the T-cell antigen receptor are structurally related to immunoglobulin molecules.1 The receptor for antigen on most T cells is formed by two polypeptides, termed α and β, that are linked to each other via disulfide bonds and associated with a collection of invariant proteins called invariant CD3 proteins (see Chap. 15). Following the rule of allelic exclusion, the T-cell receptor is clonally distributed, each T cell expressing a ...

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