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 consists of at least six different polypeptides. We have recently demonstrated that the CD3-delta subunit cannot substitute for the CD3-gamma subunit in TcR cell surface expression, in spite of significant amino acid homology between these two subunits. To identify CD3-gamma-specific domains that are required for assembly of the complete TcR and for surface expression and function of the TcR, chimeric CD3-gamma/CD3-delta molecules were constructed and expressed in T cells devoid of endogenous CD3-gamma. Substitution of the extracellular domain of CD3-gamma with that of CD3-delta did not allow cell surface expression of the TcR. In contrast, substitution of the transmembrane and/or the intracellular domains of CD3-gamma with those of CD3-delta did allow TcR cell surface expression. These results conclusively demonstrate that the extracellular domain of CD3-gamma plays a unique role in TcR assembly. Functional analyses of the transfectants demonstrated that the intracellular domain of CD3-gamma 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.
Wegener
A M
AM
Institute of Medical Microbiology and Immunology, University of Copenhagen, Panum Institute, Denmark.
Hou
X
X
Dietrich
J
J
Geisler
C
C
D017252:CD3 Complex / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D015536:Down-Regulation; D006801:Humans; D019000:Phosphotyrosine; D011493:Protein Kinase C / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; D011493:Protein Kinase C