T Cell Receptor a

Tak W Mak, The Ontario Cancer Institute, Toronto, Ontario, Canada

The importance of thymus-derived lymphocytes (T cells) in mediating the cellular basis of the immune response was recognized in the early 1960s. Independently, J. F. A. P. Miller, R. A. Good and B. Waks-man and their colleagues observed that neonatal thymectomy of mice, or thymoma development in humans, led to a reduced ability to synthesize antibodies, reject grafts, and develop delayed-type hypersensitivity.

During the late 1960s and 1970s, many investigators built a vast body of evidence supporting the role of T cells in helping B lymphocytes to generate antibody responses (T-B cell cooperation). Certain T cells also provided similar helper-effector cell assistance to a different subset of T cells responsible for cell-mediated responses. The first population of T cells is known as the helper T lymphocytes (TH) while the latter subset of T effectors are the cytotoxic (or killer) T lymphocytes (CTLs). It is now known that there are distinct subpopulations of helper T cells that can secrete specialized panels of cytokines.

The specificity of the helper and effector functions, as well as the finding that only a very few T lymphocytes could react to a given antigen, led to the conclusion that these thymus-derived cells (like their B lymphocyte counterparts) also carried antigen-specific receptors. The cell-bound antigen recognition structure on T lymphocytes is the T cell receptor (TCR). Upon specific interaction of the T cell receptor with its ligand(s), signals are transduced through the plasma membrane. This transduction results in activation of the lymphocyte, followed either by the initiation of cell division and the secretion of cytokines (Tn), or by lysis of the target cell (CTLs).

Thus, the specific recognition of antigens by the T cell receptor controls the activation and suppression of the specific immunity compartment. However, despite its importance, the identification of the genes for the T cell receptor, the elucidation of its molecular structure, and an understanding of the mechanism by which T cells generate their diversity, remained elusive throughout the 1970s and earlv 1980s.

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