Immunogenicity of B chain in insulin responder and nonresponder mice.
The potential immunogenicity of insulin B chain in beef insulin low-responder H-2k,a and high-responder H-2b,d mice was examined using lymph node proliferation assays. Oxidized B chain was immunogenic in H-2k,a, but not H-2b,d, mice. The T cell population recognized a determinant in OX-B chain associated with I-Ak. These cells did not respond to intact insulin, suggesting that the B chain determinant was not available to I-Ak during immunologic processing of insulin. Responses were observed in H-2k and H-2d, but not H-2b, after immunization with reduced and carboxyamidomethylated-insulin which contains equimolar A chain and B chain. These responses were I-A-restricted and heterogeneous, with reactivity to A chain and B chain determinants. In each case, little or no cross-reactivity was observed between RCAM-insulin and intact insulin. Furthermore, T cell populations induced in H-2k mice selectively recognized OX-B chain or RCAM-B chain, which differ in chemical modification of the thiols of Cys B7 and Cys B19. Similarly, RCAM-BINS-immune T cells from H-2d did not react to OX-B chain. These results indicate that derivatization of the cysteine thiols, through disulfide bonds, oxidation, or carboxyamidomethylation, radically affects T cell recognition of insulin B chain.
Department of Pathology, Emory University School of Medicine, Atlanta, Georgia 30322.
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Jensen
D000818:Animals; D002417:Cattle; D000939:Epitopes; D006183:H-2 Antigens / Q000276:immunology; D007328:Insulin / Q000276:immunology*; D046911:Macromolecular Substances; D051379:Mice; D008817:Mice, Mutant Strains; D010084:Oxidation-Reduction; D010455:Peptides / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D006183:H-2 Antigens; D007328:Insulin; D046911:Macromolecular Substances; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D013438:Sulfhydryl Compounds