In vitro mutagenesis at a single residue introduces B and T cell epitopes into a class I HLA molecule.
We have studied the interaction of HLA class I antigens with alloreactive cytotoxic T lymphocytes and monoclonal antibodies using site-directed mutagenesis and expression of an HLA-Aw68.1 gene. Two mutants containing distinct substitutions at polymorphic residues near the NH2-terminal end of the alpha 2 domain were made. One mutant with substitutions at positions 95 and 97 corresponding to residues found in HLA-A2.1 showed no alterations in binding of HLA-Aw68- or HLA-A2-specific monoclonal antibodies, but was reactive with some HLA-A2-specific CTL clones. A second mutant, in which glycine at position 107 was replaced with tryptophan found at that position in HLA-A2.1, was recognized by HLA-A2-specific CTL clones and HLA-A2, Aw69-specific monoclonal antibodies. Thus, substitution of a single amino acid residue at position 107 of the HLA-Aw68.1 molecule generates an allospecific determinant shared with HLA-A2.1 and recognized by both B and T lymphocytes.
D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D015234:HLA-A Antigens; D015789:HLA-A2 Antigen; D006801:Humans; D009154:Mutation; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000939:Epitopes; D006680:HLA Antigens; D015234:HLA-A Antigens; C053029:HLA-A*68 antigen; D015789:HLA-A2 Antigen