Experimental autoimmune thyroiditis (EAT) induced by the thyroglobulin peptide (2596-2608): influence of H-2 and non H-2 genes.
We have previously identified five thyroglobulin (Tg) peptides with Ak-binding motifs that induce experimental autoimmune thyroiditis (EAT) in CBA/J (H-2k) mice. In this study, we have examined whether H-2 or non H-2 genes can influence the immunopathogenicity of peptide p2596 (a.a. 2596-2608), which earlier elicited considerable pathology in CBA/J hosts. The p2596 peptide induced mild EAT--(infiltration index range=1-2)-- in H-2-compatible AKR/J, B10.BR, and C3H/HeJ mice. Moreover, p2596-primed LNC from these mice exhibited peptide-specific proliferative responses and secreted significant amounts of IL-2 and IFN-gamma in recall in vitro assays. Priming and boosting of these strains with p2596 resulted in the generation of specific IgG responses five weeks after the initial challenge. In contrast, s.c. challenge of H-2-incompatible strains such as DBA/1J (H-2q), SJL (H-2s), DBA/2J (H-2d) and C57BL/6 (H-2b) with the same peptide dose did not elicit EAT pathology and peptide-specific B- or T-cell responses. These data demonstrate the thyroiditogenic potential of p2596 in H-2k strains of diverse non-H-2 backgrounds but not in mice carrying H-2b, d, q or s haplotypes.
Verginis
Panayotis
P
Division of Endocrinology, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
Carayanniotis
George
G
D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005260:Female; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology; D051379:Mice; D010446:Peptide Fragments / Q000276:immunology*; D013954:Thyroglobulin / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000139:chemically induced* / Q000276:immunology
D000939:Epitopes; D006183:H-2 Antigens; D010446:Peptide Fragments; D013954:Thyroglobulin