Much as B cells use the B-cell receptors on their surfaces to recognize antigens and generate intracellular signals that lead to clonal expansion, T cells depend on their T-cell receptors (TCRs) to initiate their participation in immune responses. T cells that have been activated via these antigen-specific receptors proliferate and acquire the capacity to kill antigen-bearing target cells (in the case of cytotoxic T cells) or to secrete cytokines that will assist B cells in their differentiation (in the case of helper T cells). The TCR recognizes antigenic peptides bound to MHC molecules.

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The TCR is composed of two glycoprotein subunits (Figure 23-29), each of which is encoded by a somatically rearranged gene. The receptor is composed of either an α and a β subunit or a γ and a δ subunit. The structure of these subunits is similar to that of the F(ab) portion of an immunoglobulin: at the N-terminal end is a variable region, followed by a constant region and a transmembrane segment. The cytoplasmic tails of the TCR subunits are short and do not directly interact with cytoplasmic signal transduction molecules. Instead, the TCR associates with the CD3 complex, a set of membrane glycoproteins composed of γ, δ, ε, and ζ chains. (The TCR γ and δ subunits are not to be confused with the similarly designated subunits of the CD3 complex.) The ε chain forms a noncovalent dimer with the γ or the δ chain to yield δε and γε complexes. The extracellular domains of the CD3 subunits are homologous to immunoglobulin domains, and the cytoplasmic domain in each contains an ITAM (immunoreceptor tyrosine-based activation motif), by which adapter proteins may be recruited upon phosphorylation of its tyrosine residues. The ζ chain is integrated into the CD3-TCR complex as a disulfide-bonded homodimer, and each ζ chain contains three ITAMs.