CONTRASTING IMMUNOPATHOGENIC PROPERTIES OF HIGHLY HOMOLOGOUS PEPTIDESFROM RAT AND HUMAN THYROGLOBULIN

The current lack of amino acid sequence data for mouse thyroglobulin ( Tg) necessitates mapping of pathogenic T-cell epitopes on heterologous Tg in mouse experimental autoimmune thyroiditis (EAT). A prevailing a ssumption has been that epitopes sharing a high degree of amino acid h omology among heterologous Tg are likely to exhibit the same immunopat hogenic properties in the same host. In this report, we have examined this concept while working with the 18-mer rat(r)Tg(2695-13) peptide t hat was previously shown to elicit A(s)-restricted T cells and EAT in SJL mice. A major immunopathogenic T-cell epitope was localized within the 12-mer rTg(2695-06). It was found that the human 12-mer homologue that carries two Ser substitutions at Glu2703 and Thr2704 exhibited c ontrasting properties: it failed to activate Th1 cells in lymphokine a nd proliferation assays; it did not cross-react with rTg(2695-06) at t he T-cell level; and it induced only focal thyroiditis following adopt ive transfer of specific lymph node cells. These data highlight the ca veat involved in extrapolating results of pathogenic T-cell epitope ma pping across heterologous Tgs, even when such epitopes share a high de gree of amino acid homology.