Human thyroglobulin peptide p2340 induces autoimmune thyroiditis in HLA-DR3 transgenic mice.
In a previous study we demonstrated that the human thyroglobulin (hTg) peptide p2340 (aa 2340-2359) can stimulate a T cell response and elicit experimental autoimmune thyroiditis (EAT) in AKR/J (H-2(k)) mice. In the present study we examined whether p2340 can induce EAT in single HLA class II DR3 transgenic mice. This peptide was found to be immunogenic at the T cell level in DR3 mice, since it induced specific proliferative responses, as well as IL-2 and IFN-gamma secretion in secondary cultures of peptide-primed lymph node cells (LNC). Immunization of HLA-DR3 mice with p2340 in CFA elicited EAT (infiltration index of 1 to 2) in eight of nine mice. Peptide-primed LNC responded to intact hTg, whereas, hTg-primed LNC did not respond to p2340 in culture, suggesting that p2340 contains subdominant T cell epitope(s). P2340 was also found to be immunogenic at the B cell level, since strong p2340-specific IgG response was detected in all transgenic mice tested. Thus, we provide evidence for a pathogenic role of an hTg peptide in HLA-DR3 transgenic mice. Therefore, p2340 could be presented by DR3 molecule in patients with Hashimoto's thyroiditis and participate in the development of the disease.
Karras
Evangelos
E
Immunology Laboratory, Department of Biochemistry, Hellenic Pasteur Institute, 127 Vasilissis Sofias Avenue, 11521 Athens, Greece.
Yang
Huan
H
Lymberi
Peggy
P
Christadoss
Premkumar
P
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015803:HLA-DR3 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000008:administration & dosage* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D013954:Thyroglobulin / Q000008:administration & dosage* / Q000276:immunology; D013961:Thyroid Gland / Q000276:immunology / Q000473:pathology; D013967:Thyroiditis, Autoimmune / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology
D001323:Autoantibodies; D018984:Epitopes, T-Lymphocyte; D015803:HLA-DR3 Antigen; D007074:Immunoglobulin G; D010455:Peptides; D013954:Thyroglobulin