DEVELOPMENTAL REGULATION OF ALPHA-BETA-T-CELL ANTIGEN RECEPTOR ASSEMBLY IN IMMATURE CD4(+)CD8(+) THYMOCYTES

Most lymphocytes of the T cell lineage develop along the CD4/CD8 pathway and express antigen receptors on their surfaces consisting of clonotypic alpha beta chains associated with invariant CD3-gamma delta epsilon components and zeta chains, collectively referred to as the T cell antigen receptor complex (TCR). Expression of the TCR complex is dynamically regulated during T cell development, with immature CD4(+)CD8(+) thymocytes expressing only 10% of the number of (alpha beta TCR complexes on their surfaces expressed by mature CD4(+) and CD8(+) T cells. Recent evidence demonstrates that low surface TCR density on CD4(+)CD8(+) thymocytes results from the limited survival of a single TCR component within the ER, the TCR alpha chain, which has a half life of only 15 minutes in immature thymocytes, compared to >75 minutes in mature T cells. Instability of TCR alpha proteins in immature CD4(+)CD8(+) thymocytes represents a novel mechanism by which expression of the multisubunit TCR complex is quantitatively regulated during T cell development. In the current review we discuss our recent findings concerning the assembly, intracellular transport, and expression of alpha beta TCR complexes in CD4(+)CD8(+) thymocytes and comment on the functional significance of TCR alpha instability during T cell development.