Session: OR28-Thyroid Autoimmunity
Room 103 (Moscone Center)
We induced experimental autoimmune thyroiditis (EAT) by immunizing the DR3 transgenic mice (both on C57BL/6 background and on NOD background which is more susceptible to EAT) subcutaneously with hTg in CFA on days 0 and 7, and sacrificed them on day 21. We then assessed T-cell responses to the 5 hTg peptides that bind in vitro to DRb1-Arg74 (Tg1951, Tg1571, Tg202, Tg726, Tg2098) using CFSE test of proliferation and evaluating their cytokine responses. In addition, we confirmed the development of EAT by determining anti-thyroglobulin antibody levels in the serum and looking for thyroidal lymphocytic infiltration.
Two of 3 NOD mice and 9 out of 21 C57BL/6 mice immunized with hTg showed T-cell responses to hTg or hTg peptides. The T-cell response was accompanied by high levels in anti-thyroglobulin antibody levels and strong cytokine response. Thyroid infiltration was also observed in the immunized NOD mice. Peptide Tg2098 showed the strongest T-cell responses in mice that developed EAT while the 4 other peptides showed lower responses.
Our studies showed that all 5 peptides that bind in vitro to HLA-DRb1-Arg74 also stimulate T-cell responses, although to a varying degree. We conclude that these 5 Tg peptides are likely to be T-cell epitopes, among which Tg2098 appears to be the major one. Our findings set the stage to designing inhibitors of binding of these hTg epitopes to HLA-DRb1-Arg74 as a potential novel therapeutic modality in AITD.
Nothing to Disclose: CWL, FM, RO, EC, YT
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