Lysine 271 in the transmembrane domain of the T-cell antigen receptor beta chain is necessary for its assembly with the CD3 complex but not for alpha/beta dimerization.
The T-cell antigen receptor (TcR) complex present on most T-cells is formed by a clone-specific disulfide-linked alpha/beta heterodimer noncovalently associated to the CD3 complex, the latter composed of five invariant polypeptides: gamma, delta, epsilon, zeta/zeta, or zeta/eta. The presence of conserved, oppositely charged, amino acids in the predicted transmembrane domains of all the subunits of the TcR.CD3 complex suggests that these residues may have a critical function in the assembly and/or stabilization of the complex. In order to analyze the role of the transmembrane-charged amino acids in the association and cell surface expression of the TcR.CD3 complex, we have carried out site-directed mutagenesis of Lys271 in the transmembrane domain of the TcR beta chain and analyzed the capacity of the altered chain to assemble in a TcR beta-negative T-cell line. Here we show that substitution of this positively charged residue by alanine or glutamine does not prevent cytoplasmic association of alpha and beta chains to form disulfide-linked heterodimers, but does abolish formation of an alpha/beta.CD3 complex and, consequently, its expression on the cell surface.
Alcover
A
A
Département d'Immunologie, Institut Pasteur, Paris, France.
Mariuzza
R A
RA
Ermonval
M
M
Acuto
O
O
D015703:Antigens, CD / Q000235:genetics*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D001483:Base Sequence; D017252:CD3 Complex; D002462:Cell Membrane / Q000276:immunology; D003001:Cloning, Molecular; D005796:Genes; D006801:Humans; D008239:Lysine; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D015183:Restriction Mapping; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D015345:Oligonucleotide Probes; D011948:Receptors, Antigen, T-Cell; D008239:Lysine