Receptor engagement transiently diverts the T cell receptor heterodimer from a constitutive degradation pathway

In the absence of ligand, the T cell receptor (TCR)/CD3 complex is continuo usly internalized and recycled to the cell surface, whereas receptor engage ment results in its down-regulation. The present study shows that the TCR a nd CD3 components follow different fates accompanying their constitutive in ternalization. Although the CD3 moiety is recycled to the cell surface, the TCR heterodimer is degraded and replaced by newly synthesized chains, Sinc e the TCR heterodimer cannot reach the cell membrane on its own, we propose a model in which recycling CD3 is transported along a retrograde pathway t o the endoplasmic reticulum, where it associates with newly made TCR. Inter estingly, engagement of the TCR CDS complex by superantigen resulted not on ly in the down-regulation of the TCR and CD3 components but also caused a t ransient stabilization of the TCR heterodimer. This suggests that TCR engag ement diverts the TCR heterodimer from a degradation to a recycling pathway . Contrary to CD3, the intracellular fate of the TCR heterodimer is thus re gulated, providing a mechanism for rapidly replacing nonfunctional TCR duri ng intrathymic development of T cells.