Rehermann B, Pasquinelli C, Mosier S M, Chisari F V
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037, USA.
J Clin Invest. 1995 Sep;96(3):1527-34. doi: 10.1172/JCI118191.
It has been suggested that immune selection pressure exerted by the cytotoxic T lymphocyte (CTL) response could be responsible for viral persistence during chronic hepatitis B virus infection. To address this question, in the current study we compared the DNA and amino acid sequences of, and the CTL responses to, multiple HLA-A2-restricted CTL epitopes in the hepatitis B virus in several HLA-A2-positive patients with acute and chronic hepatitis. Our results indicate that the CTL response to these epitopes is barely detectable in the majority of patients with chronic hepatitis. Further, we show that the weak CTL response is not secondary in infection by mutant viruses lacking these epitopes, and we show that the CTL response did not select for escape mutants in any of these patients. We conclude that an ineffective hepatitis B virus specific CTL response is the primary determinant of viral persistence in chronic hepatitis and that immune selection of viral variants is not a common event in the majority of patients.
有人提出，细胞毒性T淋巴细胞（CTL）反应施加的免疫选择压力可能是慢性乙型肝炎病毒感染期间病毒持续存在的原因。为了解决这个问题，在当前研究中，我们比较了几名急性和慢性肝炎的HLA - A2阳性患者中乙型肝炎病毒多个HLA - A2限制性CTL表位的DNA和氨基酸序列以及CTL反应。我们的结果表明，在大多数慢性肝炎患者中几乎检测不到对这些表位的CTL反应。此外，我们表明，弱CTL反应并非由缺乏这些表位的突变病毒感染所致，并且我们还表明，在这些患者中CTL反应并未选择出逃逸突变体。我们得出结论，无效的乙型肝炎病毒特异性CTL反应是慢性肝炎中病毒持续存在的主要决定因素，并且在大多数患者中，病毒变体的免疫选择并非常见事件。
