Initiation and Modulation of Signal Output from the T cell Antigen Receptor

Abstract

T lymphocytes recognize, and are triggered by, antigenic determinants displayed by accessory cells in association with major histocompatibility complex molecules. The T cell receptor for antigen is a multimeric structure consisting of a polymorphic, antigen-binding heterodimer (T_i) noncovalently associated with a series of at least 5 invariant polypeptides termed CD3 (Samelson et al., 1985; Baniyash et al., 1988). The highly polymorphic nature of the ligand binding site expressed by clonally distributed T_i heterodimers ensures the clonal nature of the T cell activation response to specific antigens. Under appropriate conditions, certain soluble stimuli (phytohemagglutinin [PHA], anti-T_i-CD3 antibodies) can mimic the physiologic ligand and activate T cells. Thus, the T_i-CD3 receptor functions both as a variable recognition element for antigens and as a ligand-activated signal transducer that couples the antigenic stimulus to the T cell activation response. Characteristic activation responses triggered in resting T cells include cell cycle entry, T-cell growth factor receptor expression, and the release of lymphokines, including interleukin 2 (IL2). The subsequent binding of IL2 and other lymphokines to receptors expressed by activated T cells provides the requisite stimuli for cellcycle progression, proliferation, and differentiation.