Effect of the substitution of critical residues on the allorecognition of HLA-B27.
The three-dimensional structure of the HLA class I molecules has highlighted the importance of the "groove" formed by the helices. We used site-directed mutagenesis to construct a series of HLA-B27 mutants with different substitutions at the sites of the conserved amino acid residues of HLA-B27 subtypes, specifically residue 77 which is thought to be critical to the binding site of the molecule, and a residue at the CD8 binding site. We formed an anti-B27 CTL line and derived six anti-B27 clones. Each of the six clones showed a different pattern of reaction, reflecting the diversity of the epitopes recognized. All nine mutants were effective in altering allorecognition by HLA-B27 specific CTL, although positions 45 and 77 caused the most drastic effect. The residue in position 77 is also the last amino acid of the peptide sequence shared with Klebsiella. Our results highlight the importance of certain epitopes in allorecognition that may have important implications for the immunotherapy of autoimmune diseases.
D000595:Amino Acid Sequence; D002460:Cell Line; D002469:Cell Separation; D000939:Epitopes; D005434:Flow Cytometry; D015796:HLA-B27 Antigen / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000939:Epitopes; D015796:HLA-B27 Antigen