Distinct domains of the CD3-γ chain are involved in surface expression and function of the T cell antigen receptor

Abstract

The T cell antigen receptor (TcR) is a multisubunit complex that consists of at least six different polypeptides. We have recently demonstrated that the CD3-δ subunit cannot substitute for the CD3-γ subunit in TcR cell surface expression, in spite of significant amino acid homology between these two subunits. To identify CD3-γ-specific domains that are required for assembly of the complete TcR and for surface expression and function of the TcR, chimeric CD3-γ/CD3-δ molecules were constructed and expressed in T cells devoid of endogenous CD3-γ. Substitution of the extracellular domain of CD3-γ with that of CD3-δ did not allow cell surface expression of the TcR. In contrast, substitution of the transmembrane and/or the intracellular domains of CD3-γ with those of CD3-δ did allow TcR cell surface expression. These results conclusively demonstrate that the extracellular domain of CD3- γ plays a unique role in TcR assembly. Functional analyses of the transfectants demonstrated that the intracellular domain of CD3-γ is required for protein kinase C-mediated down-regulation of TcR but is dispensable for the pattern of tyrosine phosphorylation observed following activation through TcR.