Immunological mimicry between N-acetyl-beta-D-glucosamine and cytokeratin peptides. Evidence for a microbially driven anti-keratin antibody response.

摘要: We discovered recently that a subset of mouse anti-streptococcal mAbs cross-reacted with N-acetyl-beta-D-glucosamine (GlcNAc) and certain cytoskeletal proteins, recognized both carbohydrate peptide antigenic determinants. To further study the nature biologic significance immunologic mimicry between Ags, eight human hybridomas secreting anti-GlcNAc were produced by in vitro stimulation PBL streptococcal peptidoglycan-polysaccharide complexes pokeweed mitogen. All described this shown to express marked cross-reactivity keratin from skin ELISA Western immunoblot. Mapping overlapping synthetic decapeptides entire amino acid sequence cytokeratin 14 revealed specific decapeptides. Four single decapeptide whereas two reacted several individual epitopes different fragments 14. In addition, mAbs, 1.C8 9.B12, multiple decapeptides, predominantly head domain molecule, their reactivity correlated positive binding immunoblot staining epidermis indirect immunofluorescent assay. Finally, we demonstrated Abs induced BALB/c mice immunized GlcNAc-BSA but not BSA, suggesting anti-keratin Ab response vivo may be driven nonkeratin Ags containing terminal O-linked GlcNAc.