Kulkarni A B, Müllbacher A, Parrish C R, Westaway E G, Coia G, Blanden R V
Division of Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra.
J Virol. 1992 Jun;66(6):3583-92. doi: 10.1128/JVI.66.6.3583-3592.1992.
The present paper analyzes the influence of major histocompatibility complex (MHC) class II (Ir) genes on MHC class II-restricted T-cell responses to West Nile virus (WNV) and recombinant vaccinia virus-derived Kunjin virus antigens and identifies the immunodominant Kunjin virus antigens. Generally, mice were primed by intravenous infection with WNV or Kunjin virus, and their CD4+ T cells were stimulated in vitro 14 days later with WNV or Kunjin virus antigens to pulse macrophage or B-cell antigen-presenting cells (APC). WNV-specific in vitro T-cell responses from H-2b mice were higher than those from H-2d, H-2k, and H-2q mice. When recombinant vaccinia virus-derived Kunjin virus antigen preparations were tested in vitro, Kunjin virus-immune T cells of H-2b haplotype responded most strongly to structural (prM, C, E) and membrane-associated nonstructural (NS1) proteins encoded by VKV 1031 and showed weaker responses to cytosolic nonstructural protein NS5 (VKV 1022), whereas the responders of H-2k haplotype responded most strongly to the antigens encoded by VKV 1022 and gave lesser responses to VKV 1031. H-2d T cells gave weaker responses than either H-2b or H-2k cells, with responses to VKV 1031 generally being higher than those to VKV 1022. Responses to VKV 1023 or VKV 1024 encoding all of the NS3 to NS5 gene sequence or to VKV 1023 encoding all of NS3 were weak or absent. Within a given inbred strain, B cells and macrophages differed in their abilities to present recombinant vaccinia virus-derived Kunjin virus antigens, both in terms of magnitude of T-cell responses induced and the particular Kunjin virus protein presented. T cells from different non-MHC genetic backgrounds varied in their requirements of macrophage numbers as APC for maximum reactivity, suggesting that the concentration of class II MHC antigens and other molecules affecting APC-T-cell interaction varied in mice with different genetic backgrounds. Regardless of MHC haplotype, responses to VKV 1024, which encompasses VKV 1023 and VKV 1022, were either absent or lower than those to VKV 1022, possibly reflecting differences in the processing requirements of these two proteins. When mice were primed intravenously with recombinant vaccinia virus and when their CD4+ T cells were stimulated in vitro with native Kunjin virus antigens, VKV 1031 primed more efficiently than Kunjin virus and VKV 1022 primed similarly to Kunjin virus.
本文分析了主要组织相容性复合体（MHC）Ⅱ类（Ir）基因对MHCⅡ类限制性T细胞针对西尼罗河病毒（WNV）和重组痘苗病毒衍生的库京病毒抗原的反应的影响，并确定了免疫显性的库京病毒抗原。一般来说，小鼠通过静脉注射WNV或库京病毒进行免疫，14天后用WNV或库京病毒抗原在体外刺激其CD4 + T细胞，以刺激巨噬细胞或B细胞抗原呈递细胞（APC）。H-2b小鼠的WNV特异性体外T细胞反应高于H-2d、H-2k和H-2q小鼠。当对重组痘苗病毒衍生的库京病毒抗原制剂进行体外测试时，H-2b单倍型的库京病毒免疫T细胞对VKV 1031编码的结构蛋白（prM、C、E）和膜相关非结构蛋白（NS1）反应最强，对胞质非结构蛋白NS5（VKV 1022）反应较弱，而H-2k单倍型的反应者对VKV 1022编码的抗原反应最强，对VKV 1031反应较小。H-2d T细胞的反应比H-2b或H-2k细胞弱，对VKV 1031的反应通常高于对VKV 1022的反应。对编码所有NS3至NS5基因序列的VKV 1023或VKV 1024或对编码所有NS3的VKV 1023的反应较弱或无反应。在给定的近交系中，B细胞和巨噬细胞在呈递重组痘苗病毒衍生的库京病毒抗原的能力方面存在差异，这体现在诱导的T细胞反应强度和所呈递的特定库京病毒蛋白方面。来自不同非MHC遗传背景的T细胞对作为APC的巨噬细胞数量的要求不同，以实现最大反应性，这表明在具有不同遗传背景的小鼠中，Ⅱ类MHC抗原和其他影响APC-T细胞相互作用的分子的浓度有所不同。无论MHC单倍型如何，对包含VKV 1023和VKV 1022的VKV 1024的反应要么不存在，要么低于对VKV 1022的反应，这可能反映了这两种蛋白在加工要求上的差异。当小鼠通过静脉注射重组痘苗病毒进行免疫，并且其CD4 + T细胞在体外被天然库京病毒抗原刺激时，VKV 1031比库京病毒更有效地启动免疫，而VKV 1022与库京病毒启动免疫的效果相似。
