Amino acid substitutions in the first complementarity-determining region of a murine T-cell receptor alpha chain affect antigen-major histocompatibility complex recognition.
The T-cell antigen receptor mediates recognition of foreign antigens physically associated with major histocompatibility complex (MHC) proteins. The tertiary structure of the T-cell receptor is thought to resemble that of immunoglobulin Fab fragments and to possess corresponding complementarity-determining regions (CDRs) that contact antigen-MHC. To test such a model for the T-cell receptor, we have generated T-cell hybridomas that express a wild-type or mutant form of the T-cell receptor present on the p-azobenzenearsonate-specific T-cell clone D5. Mutation of 2 amino acids (Tyr26 to serine, Gly28 to valine) in the predicted CDR1 of the D5 T-cell receptor alpha chain caused a markedly diminished response to antigen without affecting the response to anti-CD3 and anti-T-cell receptor antibodies. These results constitute the first test of the prediction that CDR1 in the T-cell receptor alpha chain is important for antigen-MHC recognition, thus providing strong evidence for the structural model of the T-cell antigen receptor based upon immunoglobulin.
Nalefski
E A
EA
Division of Tumor Virology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Wong
J G
JG
Rao
A
A
D000595:Amino Acid Sequence; D000936:Antigen-Antibody Complex; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001483:Base Sequence; D015139:Blotting, Southern; D017252:CD3 Complex; D002460:Cell Line; D005434:Flow Cytometry; D006649:Histocompatibility Antigens / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007700:Kinetics; D008285:Major Histocompatibility Complex; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids; D011487:Protein Conformation; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D006649:Histocompatibility Antigens; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell