Characterization of a novel H2A(-)E(+) transgenic model susceptible to heterologous but not self thyroglobulin in autoimmune thyroiditis: Thyroiditistransfer with V beta 8(+) T cells

Recently we reported on a novel H2E transgenic, IA-negative model of experi mental autoimmune thyroiditis (EAT) that excludes reactivity to self in its susceptibility pattern to heterologous thyroglobulin (Tg). In conventional , susceptible mouse strains, EAT is inducible with both homologous and hete rologous Tg; e.g., human (h)Tg shares conserved thyroiditogenic epitopes wi th mouse (m)Tg. However, when an H2Ea(k) transgene is introduced into class II-negative B10.Ab(0) mice, which express neither surface IA (mutant A bet a -chain) nor surface IE (nonfunctional Ea gene), the resultant H2E(b) mole cules are permissive for EAT induction by hTg, but not self mTg. Also, the hTg-primed cells do not cross-react with mTg. To explore this unique capacity of E(+)B10.Ab(0) mice to distinguish self f rom nonself Tg, we have developed T cell lines to examine the T cell recept or repertoire and observed a consistent V beta8(+) component after repeated hTg stimulation. Enrichment and activation of V beta8(+) T cells by either superantigen staphylococcal entertoxin B or anti-V beta8 in vitro enabled thyroiditis transfer to untreated A(-)E(+) recipients, similar to hTg activ ation. V beta8(+) T cells isolated by FACS from hTg-immunized mice also pro liferated to hTg in vitro. These studies support the contribution of V beta 8 genes to the pathogenicity of hTg in this H2A(-)E(+) transgenic model. (C ) 2001 Academic Press.