Induction of murine thyroiditis by a non dominant E(k)-restricted peptide of human thyroglobulin.
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 Ek-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-2k) 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-gamma secretion in secondary cultures of peptide-primed lymph node cells (LNC). The p2340-specific proliferation was blocked almost completely by an Ek-specific monoclonal antibody (mAb) but was unaffected by a control Ak-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.
Karras
Evangelos
E
Immunology Laboratory, Department of Biochemistry, Hellenic Pasteur Institute, Athens, Greece.
Carayanniotis
George
G
Lymberi
Peggy
P
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000032:analysis; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008806:Mice, Inbred AKR; D010446:Peptide Fragments / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D013954:Thyroglobulin / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000276:immunology* / Q000473:pathology
D001323:Autoantibodies; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D007376:Interleukin-2; D010446:Peptide Fragments; D007371:Interferon-gamma; D013954:Thyroglobulin