Original antigenic sin impairs cytotoxic T lymphocyte responses to viruses bearing variant epitopes
Original antigenic sin impairs cytotoxic T lymphocyte responses to viruses bearing variant epitopes
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DOI：
10.1038/28860
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发表时间：
1998-07-30
期刊：
影响因子：
64.8
通讯作者：
Zinkernagel, RM
中科院分区：
文献类型：
--
作者：
Klenerman, P;Zinkernagel, RM
一些病毒，包括人类免疫缺陷病毒（HIV）和乙型肝炎病毒（HBV），以及小鼠淋巴细胞脉络丛脑膜炎病毒（LCMV），最初是由细胞毒性T淋巴细胞（ctl）控制的，但随后可能通过相关T细胞表位的突变而逃逸（1-3），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，但对T细胞抗原受体呈现改变的表面（4,5）。这些所谓的改变肽配体在体内的确切作用尚不清楚。在这里，我们报告了LCMV-WE菌株引发的小鼠对we衍生的CTL表位变体的后续感染的反应，其CTL反应针对初始表位而不是针对新的变异表位。这种“原始抗原原原性”现象最初在流感中被描述（6-8），是一种由暴露于先前存在的菌株确定的保护性抗体交叉反应的不对称模式，因此可能扩展到某些CTL反应。CTL对感染同一个体的变异病毒的清除受损，从而可能增强变异病毒在个体宿主中进化的免疫逃逸。
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(1-3), 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(4,5). 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(6-8) 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.