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Induction of murine thyroiditis by a non dominant E k ‐restricted peptide of human thyroglobulin
Author(s) -
Karras Evangelos,
Carayanniotis George,
Lymberi Peggy
Publication year - 2003
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2003.01607.x
Subject(s) - thyroglobulin , epitope , peptide , monoclonal antibody , thyroiditis , autoimmune thyroiditis , microbiology and biotechnology , biology , t cell , endocrinology , antibody , medicine , in vivo , immunology , thyroid , immune system , biochemistry , genetics
Summary We 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 specific proliferative responses as well as interleukin‐2 and interferon‐γ secretion in secondary cultures of peptide‐primed lymph node cells (LNC). The p2340‐specific proliferation was blocked almost completely by an E k ‐specific monoclonal antibody (mAb) but was unaffected by a control A k ‐specific 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 T‐cell epitope(s). Direct subcutanaeous challenge of AKR/J mice ( n = 9) with p2340 in adjuvant, elicited mild to moderate EAT (infiltration index of 1–2) and strong p2340‐specific immunoglobulin G responses in all mice tested. These data delineate a new thyroiditogenic sequence within the carboxyl terminal region of hTg.