Dissection of the Role of CD3γ Chains in Profound but Reversible T‐Cell Receptor Down‐regulation

T‐lymphocyte activity in the immune system is regulated by the quantity of surface membrane T‐cell antigen receptors (TCR). The amount of surface‐bound TCR is dependent on the rate of [ 1] biosynthesis, assembly and intracellular transport of the individual chains composing the TCR/CD3 complex and [ 2] the internalization and recycling of the receptors. The TCR–ligand interaction augments receptor internalization. In the present paper, we have studied short‐ and long‐term down‐regulation of TCR/CD3 complexes with monoclonal anti‐TCR/CD3 antibodies, and attempted to determine which component(s) of the TCR/CD3 complex are responsible for these two phenomena. Our data indicate that short‐ and long‐term down‐regulation is mediated by different mechanisms, and that the extracellular and/or transmembrane regions of CD3γ molecules appear to play an important role in chronic TCR/CD3 down‐regulation and subsequent deficient re‐expression. These results may have important implications for the understanding of induction of T‐cell tolerance or anergy.