CHARACTERIZATION OF SELF-REACTIVE T-CELLS THAT EVADE TOLERANCE IN HEPATITIS-B E-ANTIGEN TRANSGENIC MICE

Previous studies of hepatitis B e antigen (HBeAg)-expressing transgeni c (Tg31e) mice have indicated that the degree of T cell tolerance was epitope specific. For example, T cells specific for residues 120-133 o f HBeAg are profoundly tolerant, whereas a proportion of T cells speci fic for residues 129-140 escape tolerance induction in B10. S x B10-Tg 3le mice. To understand the basis for differential tolerance towards t wo T cell sites on the same self antigen, we characterized T cell reco gnition of HBeAg by primary T cells and T cell hybridomas derived from HBeAg-Tg and non-Tg mice. The self-reactive T cells surviving in B10- Tg3le mice exhibited a unique fine specificity albeit still focussed o n HBeAg residues 129-140, which could be distinguished from the HBeAg- specific T cell repertoire in non-Tg B10 mice. Further, self-reactive T cells were comprised predominantly of Th2-type cells that preferenti ally evaded tolerance induction as compared to their Th1 counterparts. Because HBeAg may act as a tolerogen during the vertical transmission of chronic hepatitis B virus (HBV) infection, these results suggest t hat a predominance of HBeAg-specific Th2 cells expressing a limited re pertoire may influence the initiation or the maintenance of the HBV ch ronic carrier state.