ME-Derived eα52-68 peptide presented by 112Ab interferes with clonal deletion of autoreactive T cells in autoimmune thyroiditis

Susceptibility and resistance to experimental autoimmune thyroiditis is encoded by MHC H2A genes. We reported that traditionally resistant B10 (H2(b)) mice permit thyroiditis induction with mouse thyroglobulin (mTg) after depleting regulatory T cells (Tregs), supportin A(b) presentation to thyroiditogenic T cells. Yet, Ea(k) transgenic mice, expressing Ab and normally absent E-b molecules (E(+)B10 mice), are susceptible to thyroiditis induction without Treg depletion. To explore the effect of E-b expression on mTg presentation by A(b), seven putative A(b)-binding, 15-16-mer peptides were synthesized. Five were immunogenic for both B10 and E(+)B10 mice. The effect of E-b expression was tested by competition with an E alpha 52-68 peptide, because E alpha 52-68 occupies similar to 15% of A(b) Molecules in E(+)B10 mice, binding with high affinity. E alpha 52-68 competitively reduced the proliferative response to mTg, mTg1677, and mTg2342 of lymph node cells primed to each Ag. Moreover, mTg1677 induced mild thyroiditis in Treg-depleted B10 mice, and in E(+)B10 mice without the need for Treg depletion. Ea52-68 competition with mTg-derived peptides may impede clonal deletion of pathogenic, mTg-specific T cells in the thymus.