TCRα-CD3δϵ association is the initial step in αβ dimer formation in murine T cells and is limiting in immature CD4+CD8+ thymocytes

AbstractThe present study has examined the molecular events leading to formation of αβ dimers in normal murine thymocytes and mature T cells. We demonstrate that TCR assembly proceeds by initial association of TCRα with CD3δϵ proteins and by association of TCRβ with CD3γϵ proteins to form αδϵ and βγϵ trimers; these trimers then associate to form αδϵ-βγϵ complexes, within which α-β disulfide bond formation occurs. We also show that TCR-associated protein (TRAP) associates uniquely with CD3γϵ pairs and that formation of βγϵ trimers occurs subsequent to TRAP dissociation. Importantly, we document that the assembly step that is quantitatively limiting in CD4+CD8+ thymocytes is the initial association of TCRα with CD3δϵ chains, which appears necessary to protect nascent TCRα proteins from accelerated degradation within the ER of immature thymocytes