Milich D R, Schödel F, Peterson D L, Jones J E, Hughes J L
Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
Eur J Immunol. 1995 Jun;25(6):1663-72. doi: 10.1002/eji.1830250628.
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.
先前对表达乙肝e抗原（HBeAg）的转基因（Tg31e）小鼠的研究表明，T细胞耐受程度具有表位特异性。例如，对HBeAg第120 - 131位氨基酸残基特异的T细胞具有深度耐受性，而在B10.S×B10 - Tg31e小鼠中，一部分对第129 - 140位氨基酸残基特异的T细胞能够逃避耐受诱导。为了理解对同一自身抗原上两个T细胞位点的不同耐受性的基础，我们通过从HBeAg转基因和非转基因小鼠中获得的原代T细胞和T细胞杂交瘤来表征T细胞对HBeAg的识别。存活于B10 - Tg31e小鼠中的自身反应性T细胞表现出独特的精细特异性，尽管仍集中于HBeAg的第129 - 140位氨基酸残基，这与非转基因B10小鼠中的HBeAg特异性T细胞库不同。此外，自身反应性T细胞主要由Th2型细胞组成，与它们的Th1对应细胞相比，这些细胞优先逃避耐受诱导。由于HBeAg在慢性乙型肝炎病毒（HBV）感染的垂直传播过程中可能充当耐受原，这些结果表明，表达有限库的HBeAg特异性Th2细胞占优势可能会影响HBV慢性携带者状态的起始或维持。
