DISTINCT DOMAINS OF THE CD3-GAMMA CHAIN ARE INVOLVED IN SURFACE EXPRESSION AND FUNCTION OF THE T-CELL ANTIGEN RECEPTOR

The T cell antigen receptor (TcR) is a multisubunit complex that consi sts of at least six different polypeptides. We have recently demonstra ted that the CD3-delta subunit cannot substitute for the CD3-gamma sub unit in TcR cell surface expression, in spite of significant amino aci d homology between these two subunits. To identify CD3-gamma-specific domains that are required for assembly of the complete TcR and for sur face expression and function of the TcR, chimeric CD3-gamma/CD3-delta molecules were con structed and expressed in T cells devoid of endogen ous CD3-gamma. Substitution of the extracellular domain of CD3-gamma w ith that of CD3-delta did not allow cell surface expression of the TcR , In contrast, substitution of the transmembrane and/or the intracellu lar domains of CD3-gamma with those of CD3-delta did allow TcR cell su rface expression. These results conclusively demonstrate that the extr acellular domain of CD3-gamma plays a unique role in TcR assembly. Fun ctional analyses of the transfectants demonstrated that the intracellu lar domain of CD3-gamma is required for protein kinase C-mediated down -regulation of TcR but is dispensable for the pattern of tyrosine phos phorylation observed following activation through TcR.