The human T-cell receptor

Abstract

Recent studies using cloned antigen-specific T lymphocytes and monoclonal antibodies directed at their various surface glycoprotein components have led to the identification of the human T-cell antigen receptor as a surface complex comprised of a clonotypic 90-kD Ti heterodimer and the invariant 20- and 25-kD T3 molecules. Approximately 30,000-40,000 Ti and T3 molecules exist on the surface of human T lymphocytes. These glycoproteins are acquired and expressed during late thymic ontogeny, thus providing the structural basis for immunologic competence. The alpha and beta subunits of Ti bear no precursor-product relationship to one another and are encoded by separate genes. Moreover, the presence of unique peptides following proteolysis of different Ti molecules isolated by non-cross-reactive anticlonotypic monoclonal antibodies supports the notion that variable regions exist within both the alpha and the beta subunits. N-Terminal amino acid sequencing and molecular cloning of the Ti beta subunit further show that it bears an homology to the first V-region framework of immunoglobulin light chains and represents the product of a gene that rearranges specifically in T lymphocytes. Triggering of the T3-Ti receptor complex gives rise to specific antigen-induced proliferation through an autocrine pathway involving endogenous IL-2 production, release, and subsequent binding to IL-2 receptors. The implications of these findings for understanding human T-cell growth and its regulation in disease states are discussed.

Enhanced CD3‐mediated T lymphocyte proliferation in patients with systemic lupus erythematosus

“…In marked contrast, PHA-driven responses were diminished in lymphocytes from the SLE patients. Activation via the CD3 complex mimics events that occur after binding of antigen to the TCR heterodimer, including activation of protein kinase C and intracellular Ca++ movement (21,22). These events are followed by increased transcription of messenger RNA for IL-2 and IL-2R and expanded clonal proliferation.…”

“…Key subcellular events occurring after stimulation via the CD3 complex are intracellular Ca++ movement and protein kinase C activation, which are triggered by antigen binding to TCR and IL-1, respectively (21,22). Both effects can be mimicked in vitro by calcium ionophore and phorbol esters (32,33).…”

“…Multiple lines of evidence at the molecular level link the T C R heterodimer to the antigen recognition site. After antigen binding, the noncovalently linked CD3 polypeptide complex transduces signals at a subcellular level, thus triggering the cascade of biochemical events necessary for T cell activation and proliferation (21,22). Murine MAb specific for t h e C D 3 complex can mimic these effects in vitro and provide a valuable tool for examining T cell responses in health a n d disease states.…”

“…T h e recent characterization of the TCIUCD3 complex as the structure involved in antigen recognition and transmembrane signal transduction (21,22) has greatly contributed to our understanding of the T cell activation process. Multiple lines of evidence at the molecular level link the T C R heterodimer to the antigen recognition site.…”

T cell receptor alpha-chain gene rearrangements in B-precursor leukemia are in contrast to the findings in T cell acute lymphoblastic leukemia. Comparative study of T cell receptor gene rearrangement in childhood leukemia.

“…Three T cell-specific gene families, a-, 13-, and y-chain genes, that rearrange during somatic development have been characterized (12)(13)(14)(15)(16) chains (17,18). The protein product of the y-chain gene may also be associated with the T3 complex, but in conjunction with a putative TCR 6 protein instead of the a-or f3-polypeptides.…”