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 continuously internalized and recycled to the cell surface, whereas receptor engagement results in its down-regulation. The present study shows that the TCR and CD3 components follow different fates accompanying their constitutive internalization. Although the CD3 moiety is recycled to the cell surface, the TCR heterodimer is degraded and replaced by newly synthesized chains. Since 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 to the endoplasmic reticulum, where it associates with newly made TCR. Interestingly, engagement of the TCR.CD3 complex by superantigen resulted not only in the down-regulation of the TCR and CD3 components but also caused a transient stabilization of the TCR heterodimer. This suggests that TCR engagement diverts the TCR heterodimer from a degradation to a recycling pathway. Contrary to CD3, the intracellular fate of the TCR heterodimer is thus regulated, providing a mechanism for rapidly replacing nonfunctional TCR during intrathymic development of T cells.
San José
E
E
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Cantoblanco, Madrid 28049, Spain.
Alarcón
B
B
D017252:CD3 Complex / Q000378:metabolism; D002460:Cell Line; D019281:Dimerization; D015536:Down-Regulation; D004705:Endocytosis; D006868:Hydrolysis; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000378:metabolism*
D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell