T cell receptor α‐chain tail is required for protein kinase C‐mediated down‐regulation, but not for signaling

AbstractAntigen stimulation through the T cell receptor (TCR) induces phosphorylation of the associated CD3 γδσ‐ and ζ‐chain cytoplasmic tails. These events lead to the induction of the intracellular signaling pathways with concomitant receptor down‐regulation. The TCR is down‐regulated from the cell surface by the activation of protein kinase C (PKC) and subsequent serine phosphorylation of the CD3 γ‐chain. We report here that the TCR α‐chain cytoplasmic tail is also necessary for PKC‐mediated internalization of the TCR complex. The requirement for the TCR α‐chain cytoplasmic tail is specific for internalization of the TCR complex, since down‐regulation of CD4 is still intact in hybridoma cells expressing a tailless TCR α‐chain. The absence of TCR internalization directly correlates with defective PKC‐mediated phosphorylation of the CD3 γ‐chain. Despite deficient PKC‐mediated TCR down‐regulation, the tailless αβ TCR still transduces antigenic signals resulting in the production of interleukin‐2. Although the TCR tails are not obviously required for signal transduction, the TCR α‐tail may serve as a targeting domain for PKC‐mediated down‐regulation of the TCR complex.