SUMMARYWe have previously shown that the human thyroglobulin (hTg) 20-mer peptide p2340 (aa 2340± 2359) contains an epitope recognized by Tg-reactive B cells in patients with Graves' disease. The presence of several E k -binding motifs within p2340 prompted us to examine whether this peptide can stimulate a T-cell response and elicit experimental autoimmune thyroiditis (EAT) in AKR/J (H-2 k ) mice. The peptide was found to be immunogenic at the T-cell level since it induced speci®c proliferative responses as well as interleukin-2 and interferon-g secretion in secondary cultures of peptide-primed lymph node cells (LNC). The p2340-speci®c proliferation was blocked almost completely by an E k -speci®c monoclonal antibody (mAb) but was unaffected by a control A kspeci®c mAb. Peptide-primed LNC did not respond to intact hTg and conversely, LNC primed in vivo with hTg did not respond to p2340 in culture, suggesting that p2340 contains non-dominant Tcell epitope(s). Direct subcutanaeous challenge of AKR/J mice (n 9) with p2340 in adjuvant, elicited mild to moderate EAT (in®ltration index of 1±2) and strong p2340-speci®c immunoglobulin G responses in all mice tested. These data delineate a new thyroiditogenic sequence within the carboxyl terminal region of hTg.

Summary We have previously identified a 20‐mer peptide of human thyroglobulin (hTg), p2340 (aa2340–2359), which induced experimental autoimmune thyroiditis (EAT) in AKR/J (H‐2k) and HLA‐DR3 transgenic mice. In this study, we investigated the thyroiditogenic potential of p2340 in ‘high responder’ CBA/J (H‐2k) and SJL/J (H‐2s) or ‘low responder’ C57BL/6 (H‐2b) and BALB/c (H‐2d) mice. Mice were immunized subcutaneously with 100 nmol of p2340 in complete Freund's adjuvant (CFA) and both the proliferative capacity of their lymph node cells in the presence of p2340 or intact Tg and the production of peptide‐specific antibodies were investigated. The p2340 peptide was found to contain B‐cell and non‐dominant T‐cell epitope(s) in all strains tested. Moreover, it elicited EAT in CBA/J (2/6, infiltration index (I.I.) 1) and SJL/J (5/5, I.I. 1‐3) mice after direct challenge and in BALB/c (4/7, I.I. 1) and C57BL/6 (1/5, I.I. 1) after adoptive transfer of p2340‐primed lymph node cells. P2340 is the first Tg peptide found to be pathogenic in low as well as high responder mouse strains and thus will allow us to investigate mechanisms of EAT induction in a genetically resistant host.

No abstract