PRIMARY HORMONOGENIC SITES AS CONSERVED AUTOEPITOPES ON THYROGLOBULININ MURINE AUTOIMMUNE-THYROIDITIS - ROLE OF MHC CLASS-II

A few synthetic peptides corresponding to amino acid sequences on huma n thyroglobulin (Tg) have been reported to induce moderate thyroiditis or activate mouse Tg (MTg)-primed T cells to transfer thyroiditis in mice susceptible to experimental autoimmune thyroiditis, Using three p airs of 12-mer peptides (1-12, 2549-2560, 2559-2570), with thyroxine ( T4) or noniodinated thyronine (T0) at the conserved, hormonogenic site 5, 2553, or 2567 respectively, we reported that iodination was not re quired for a Tg hormonogenic site to be a thyroiditogenic autoepitope. To determine the relative importance of MHC class II and T cell recep tor (TCR) repertoire, we compared two EAT-susceptible k and s (CBA and A.SW) haplotypes and their respective MHC-identical strain (C57BR and SJL) with similar to 50% genomic deletion of TCR V beta genes. Wherea s k and s strains develop MTg-induced EAT, vigorous immunization with peptides containing T4 or T0 at either 5 or 2553, but not at 2567, led to mild (10-20%) thyroiditis only in some mice of either k strain. TC R V beta gene differences played a minor role, T cell responses to all peptide pairs were quite similar in CBA and C57BR mice, and both hT0( 2553) and hT4(2553) reciprocally primed and stimulated their T cells, In adoptive transfer, SJL mice were somewhat more responsive to peptid e activation than A.SW but much weaker than k strains. By comparing T4 - and T0-containing peptides in different haplotypes, we show further that antigenicity of conserved hormonogenic sites is intrinsic, depend ent more on amino acid sequence and binding to appropriate class II mo lecules and less on TCR repertoire or iodination of T0. (C) 1997 Acade mic Press.