Lobigs M, Arthur C E, Müllbacher A, Blanden R V
Division of Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra.
Virology. 1994 Jul;202(1):195-201. doi: 10.1006/viro.1994.1335.
Vaccinia virus recombinants encoding regions of the Murray Valley encephalitis virus (MVE) genome, which together cover the entire viral coding region, were employed to identify the MVE protein which is the dominant source of CD8+, cytotoxic, T cell antigenic determinant(s) presented by the mouse H-2Kk major histocompatibility antigen. MVE and West Nile virus-immune, H-2k-restricted, effector cells recognized peptides derived from the MVE nonstructural polyprotein segment, and in this region the immunodominant determinant mapped to protein NS3. Interestingly, mapping of cytotoxic T cell antigenic determinants of other flaviviruses also identified the NS3 protein as the dominant source of antigenic peptides (A. B. Hill, A. Müllbacher, C. Parrish, G. Coia, E. G. Westaway, and R. V. Blanden, 1992, J. Gen. Virol. 73, 1115-1123; A. L. Rothman, I. Kurane, C.-J. Lai, M. Bray, B. Falgout, R. Men, and F. A. Ennis, 1993, J. Virol. 67, 801-806). Using an allele-specific peptide motiff for H-2Kk, we predicted 12 peptides in the MVE NS3 protein as ligands for the restriction element and identified three peptides which were recognized in association with H-2Kk by MVE-immune cytotoxic T cells. We also examined the effect of proteolytic processing in the MVE nonstructural polyprotein segment mediated by the viral proteinase NS3 on antigen processing and presentation of the MVE H-2Kk-restricted T cell determinant. Processing of the MVE polyprotein by the viral proteinase did not markedly influence the availability of this peptide determinant.
编码墨累谷脑炎病毒（MVE）基因组区域的痘苗病毒重组体，共同覆盖了整个病毒编码区，被用于鉴定由小鼠H-2Kk主要组织相容性抗原呈递的CD8⁺细胞毒性T细胞抗原决定簇的主要来源的MVE蛋白。MVE和西尼罗河病毒免疫的、H-2k限制的效应细胞识别源自MVE非结构多聚蛋白片段的肽段，并且在该区域免疫显性决定簇定位到蛋白NS3。有趣的是，其他黄病毒的细胞毒性T细胞抗原决定簇的定位也确定NS3蛋白是抗原肽的主要来源（A. B. 希尔、A. 米尔巴赫、C. 帕里什、G. 科亚、E. G. 韦斯塔韦和R. V. 布兰登，1992年，《普通病毒学杂志》73卷，1115 - 1123页；A. L. 罗斯曼、I. 仓根、C.-J. 赖、M. 布雷、B. 法尔古特、R. 门和F. A. 恩尼斯，1993年，《病毒学杂志》67卷，801 - 806页）。利用针对H-2Kk的等位基因特异性肽基序，我们预测MVE NS3蛋白中有12个肽段作为限制元件的配体，并鉴定出3个肽段，它们被MVE免疫的细胞毒性T细胞与H-2Kk结合识别。我们还研究了由病毒蛋白酶NS3介导的MVE非结构多聚蛋白片段中的蛋白水解加工对MVE H-2Kk限制的T细胞决定簇的抗原加工和呈递的影响。病毒蛋白酶对MVE多聚蛋白的加工并未显著影响该肽决定簇的可用性。
