Klenerman P, Zinkernagel R M
Institute for Experimental Immunology, University Hospital, Zurich, Switzerland.
Nature. 1998 Jul 30;394(6692):482-5. doi: 10.1038/28860.
Some viruses, including human immunodeficiency virus (HIV) and hepatitis B virus (HBV) in humans, and lymphocytic choriomeningitis virus (LCMV) in mice, are initially controlled by cytotoxic T lymphocytes (CTLs), but may subsequently escape through mutation of the relevant T-cell epitope. Some of these mutations preserve the normal binding to major histocompatibility complex class I molecules, but present an altered surface to the T-cell antigen receptor. The exact role of these so-called altered peptide ligands in vivo is not clear. Here we report that mice primed with LCMV-WE strain respond to a subsequent infection by WE-derived CTL epitope variants with a CTL response directed against the initial epitope rather than against the new variant epitope. This phenomenon of 'original antigenic sin' was initially described in influenza and is an asymmetric pattern of protective antibody crossreactivity determined by exposure to previously existing strains, which may therefore extend to some CTL responses. Original antigenic sin by CTL leads to impaired clearance of variant viruses infecting the same individual and so may enhance the immune escape of mutant viruses evolving in an individual host.
一些病毒，包括人类的人类免疫缺陷病毒（HIV）和乙型肝炎病毒（HBV），以及小鼠的淋巴细胞性脉络丛脑膜炎病毒（LCMV），最初由细胞毒性T淋巴细胞（CTL）控制，但随后可能通过相关T细胞表位的突变而逃逸。其中一些突变保留了与主要组织相容性复合体I类分子的正常结合，但呈现给T细胞抗原受体的表面发生了改变。这些所谓的改变肽配体在体内的确切作用尚不清楚。在此我们报告，用LCMV-WE株进行初次免疫的小鼠，在随后受到源自WE的CTL表位变体感染时，会产生针对初始表位而非新变体表位的CTL反应。这种“原始抗原罪”现象最初在流感中被描述，是一种由接触先前存在的毒株所决定的保护性抗体交叉反应的不对称模式，因此可能也适用于一些CTL反应。CTL引发的原始抗原罪会导致感染同一个体的变体病毒清除受损，从而可能增强在个体宿主中进化的突变病毒的免疫逃逸。
