Abstract
We have previously reported that the 17mer thyroglobulin (Tg) peptide TgP1 (a.a. 2495–2511) induces experimental autoimmune thyroiditis (EAT) inH-2 k mice, a process requiring expression ofE k genes, and inH-2 S mice that lack functional E molecules. To test whether this apparent discrepancy was due to recognition of distinct TgP1 determinants in each strain, we mapped in this study minimal T -cell epitopes within TgP1 and examined their pathogenicity in C3H (H-2 k) or SJL (H-2 S) mice. Truncation analysis using TgP1-specific, CD4+ hybridomas from C3H mice identified two overlapping determinants, (2496-2504) and (2499–2507), that were restricted by the Ek and Ak molecules, respectively. Subsequent challenge of C3H and SJL mice with these 9mer peptides revealed that the Ekrestricted (2496–2504) determinant elicited EAT and specific proliferative LNC responses in both strains, suggesting recognition in the context of As, since this is the only class II molecule expressed in SJL mice. This was further confirmed by blocking of the proliferative LNC response by an As-specific monoclonal antibody. In contrast, the Ak-restricted (2499–2507) determinant induced weak EAT and no proliferative LNC responses in either strain. These data 1) delineate the 9mer (2496–2504) peptide as a minimal Tg T-cell epitope with direct pathogenic potential in mice and 2) highlight the use of nonisotypic MHC class II molecules for the presentation of this peptide in mice of differentH-2 haplotypes.
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Rao, V.P., Balasa, B. & Carayanniotis, G. Mapping of thyroglobulin epitopes: Presentation of a 9mer pathogenic peptide by different mouse MHC class II isotypes. Immunogenetics 40, 352–359 (1994). https://doi.org/10.1007/BF01246676
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DOI: https://doi.org/10.1007/BF01246676