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 transgenic (Tg31e) mice have indicated that the degree of T cell tolerance was epitope specific. For example, T cells specific for residues 120-131 of HBeAg are profoundly tolerant, whereas a proportion of T cells specific for residues 129-140 escape tolerance induction in B10. S x B10-Tg31e mice. To understand the basis for differential tolerance towards two T cell sites on the same self antigen, we characterized T cell recognition 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-Tg31e mice exhibited a unique fine specificity, albeit still focussed on 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 preferentially 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 that a predominance of HBeAg-specific Th2 cells expressing a limited repertoire may influence the initiation or the maintenance of the HBV chronic carrier state.
Milich
D R
DR
Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
Schödel
F
F
Peterson
D L
DL
Jones
J E
JE
Hughes
J L
JL
D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D002455:Cell Division; D000939:Epitopes / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology; D007108:Immune Tolerance; D007116:Immunization, Passive; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology*
D000956:Antigens, Viral; D001323:Autoantibodies; D000939:Epitopes