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, namely CD3γ, CD3δ, CD3ε, and CD247.* These invariant proteins are necessary for 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. A small subset of T cells has 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 only if they are presented to them by defined major histocompatibility complex molecules on the plasma membrane of another cell, the antigen-presenting cell. The response of the T cell to antigen depends on the intensity of the signal generated by ligation of the T-cell receptor, and is modified by the simultaneous ligation of other accessory molecules. Interactions at the contact sites between T-cells and antigen-presenting cells 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 and/or programmed cell death.
Acronyms and Abbreviations
AP-1, activation protein-1; APC, antigen-presenting cell; CTLA-4, cytotoxic T-lymphocyte antigen 4; ERK, extracellular receptor-activated kinase; FOXP3, forkhead box P3; ICAM, intercellular adhesion molecule; IFN-γ, interferon-gamma; IL, interleukin; IPEX syndrome, immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome; ITAM, immunoreceptor tyrosine-based activation motif; ITIM, immunoreceptor tyrosine-based inhibitory motif; 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 cell; PKC, protein kinase C; PLC-γ1, phospholipase C-1 gamma; RORγt, retinoic acid-related orphan receptor γ thymus isoform; SAPK, stress-activated protein 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-LYMPHOCYTE ANTIGEN RECEPTORS
T-CELL RECEPTOR HETERODIMERS
The structural basis of T-cell recognition of antigen has been known since the 1990s, when a plethora of studies demonstrated that the proteins of the T-cell antigen receptor are structurally related to immunoglobulin molecules.1 The T-cell receptor is formed by a heterodimer, that is, two disulfide-bond-linked polypeptides that are expressed on the cell surface and are ...