Monoclonal antibodies against an HLA-B27-derived peptide react with an epitope present on bacterial proteins.
The role of molecular mimicry in the spondyloarthropathies was investigated with respect to the epitopes involved. mAb were produced against a synthetic peptide whose sequence was derived from a polymorphic region of the HLA-B27 molecule (amino acids 63-83). Two antibodies (J7F2 and H2B6) were selected for study on the basis of their ability to react with bacterial envelope proteins (ELISA) and B27-positive cells (immunofluorescence). J7F2 reacted preferentially with B27-positive cells and neither antibody reacted with MHC class I negative cells. Based on SDS-PAGE blot analysis of bacterial envelope proteins, the pattern of reactivity for both antibodies (against 36- and 19-kDa proteins) was the same as that for a third monoclonal produced against bacterial envelope and reactive with B27-positive cells. This apparent epitope similarity was investigated by using synthetic peptides to inhibit binding of the monoclonals. The B27 synthetic peptide and a smaller peptide derived from it were efficient inhibitors of antipeptide and antibacterial antibody binding to bacterial Ag and B27-positive cells. These studies provide insight into the molecular basis of cross-reactivity between bacterial proteins and MHC class I molecules.
Immunobiology Section, Food and Drug Administration, Washington, DC 20204.
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Raybourne
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Williams
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D015153:Blotting, Western; D002460:Cell Line; D003429:Cross Reactions; D000939:Epitopes; D015796:HLA-B27 Antigen / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D012763:Shigella flexneri / Q000276:immunology
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D000939:Epitopes; D015796:HLA-B27 Antigen; D010455:Peptides