The CD3ε Subunit of the TCR Contains Endocytosis Signals

Abstract

Ligand binding to TCR induces its internalization and cell surface down-modulation. These phenomena contribute to the extinction of activation signals. Due to the multicomponent nature of the TCR-CD3 complex, its internalization may be mediated by one or several of its subunits. Although it has been reported that CD3γ and CD3δ contain endocytosis motifs involved in the internalization of the TCR-CD3 complex, other subunits could also be involved in this process. For instance, CD3ε and CDζ display amino acid sequences reminiscent of internalization motifs. To investigate whether CD3ε bears endocytosis signals, we have analyzed the internalization capacity of a panel of deletion and point mutants of CD3ε that were expressed on the cell surface independently of other TCR-CD3 subunits. Here we report that CD3ε displays endocytosis determinants. These data indicate that CD3ε could contribute to the internalization and cell surface down-regulation of TCR-CD3 complexes. Moreover, the existence of endocytosis signals in this polypeptide could serve to retrieve unassembled CD3ε subunits or partial CD3 complexes from the plasma membrane, thus restricting the expression on the cell surface to fully functional TCR-CD3 complexes.