All T cells express an antigen receptor formed by two polymorphic polypeptides that are invariably associated with the CD3 complex containing CD3γ, CD3δ, CD3ε, and ζ subunits, as well as multiple accessory molecules. These proteins are necessary for surface expression and signaling by the T-cell receptor (TCR). On most T cells, the TCR is formed by α and β polypeptides. In a small T-cell subset, receptors are formed by γ and δ polypeptides. The diversity of these TCR polypeptides is comparable to that estimated for immunoglobulin (Ig) molecules. However, unlike Igs, TCR antigen recognition requires antigen presentation by defined major histocompatibility complex molecules on the plasma membrane of another cell, the antigen-presenting cell (APC). T-cell response to antigen depends on the intensity of the signal generated by ligation of the TCR and is modified by the simultaneous ligation of other accessory molecules. Interactions at the contact sites between T cells and APCs are organized in the immunologic synapse. The outcome of T-cell antigen recognition can range from immune activation and T-cell proliferation to specific T-cell tolerance or programmed cell death.
Acronyms and Abbreviations
AID, activation-induced deaminase; AIRE, autoimmune regulator gene; AP-1, activation protein-1 (AP-1); APC, antigen-presenting cell; APECED, autoimmune polyendocrine candidiasis ectodermal dystrophy syndrome; BTLA, B- and T-lymphocyte attenuator; CD, cluster of differentiation; CCL, C-C chemokine ligand; CCR, C-C chemokine receptor; CXCL, C-X-C chemokine ligand; CXCR, C-X-C chemokine receptor; CsA, cyclosporine; CTLA-4, cytotoxic T-lymphocyte antigen 4; DC, dendritic cells; EOMES, eomesodermin; ERK, extracellular receptor-activated kinase; FoxP3, forkhead box P3; FYB, FYN binding protein FYB-120/130; GATA3, trans-acting T-cell-specific transcription factor; GRAP2, GRB2-related adapter protein 2; GEF, guanine nucleotide-exchange factor; HIV, human immunodeficiency virus; HLA, human histocompatibility antigens; ICAMs, intercellular adhesion molecules; ICOS, inducible T-cell costimulator; IFN-γ, interferon gamma; Ig, immunoglobulin; IL, interleukin; IPEX syndrome, immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome; IRF, interferon regulatory transcription factor; ITAMs, immunoreceptor tyrosine-based activation motifs; ITIMs, immunoreceptor tyrosine-based inhibitory motifs; JNK, c-Jun N-terminal kinase; LAD, leukocyte adhesion deficiencies; LAG3, lymphocyte activation gene 3; LAT, linker of activation of T cells; LCP2, Lymphocyte cytosolic protein 2 (also known as SLP-76); LFA, lymphocyte-function-associated; MAP, mitogen-activated protein; MHC, major histocompatibility complex; MS, multiple sclerosis; Nck, non-catalytic region of tyrosine kinase adaptor protein 1; NFAT, nuclear factor of activated T cells; PCR, polymerase-chain-reaction; PD-1, programmed death-1; PKC, protein kinase C; PLC-γ1, phospholipase C-1 gamma; pTreg, peripherally derived regulatory T cell; RA, rheumatoid arthritis; RORγt, retinoic acid-related orphan receptor γ thymus isoform; SAP, signal lymphocyte activation molecule (SLAM)-associated protein; SH2 domain, Src homology 2 domain; SH3 domain, Src homology 3 domain; SLE, systemic lupus erythematosus; SMAC, supramolecular activation clusters; STAT, signal transducer and activator of transcription; T-ALL, T-cell acute lymphoblastic leukemia; T-BET, T-box transcription factor; TCM, central-memory T cells; TEM, effector-memory T cells Tfh cell, follicular helper T cell; TGF-β, transforming growth factor beta; Treg, CD4+CD25+ regulatory T cells; tTreg, ...