Sharma Madeva C, Zhou Wendy, Martinez Joy, Krymskaya Ludmila, Srivastava Tumul, Haq Wahajul, Diamond Don J, Lacey Simon F
Laboratory of Vaccine Research, Beckman Research Institute of the City of Hope, 1450 East Duarte Road, Duarte, CA 91010-3000, USA.
Virology. 2006 Jun 20;350(1):128-36. doi: 10.1016/j.virol.2006.02.040. Epub 2006 Apr 5.
Two HLA-A02-restricted epitopes have been identified within the VP1 polypeptide of a human polyomavirus, BK virus, which is associated with polyomavirus-associated nephropathy in kidney transplant patients. Immunization of transgenic mice with recombinant modified vaccinia Ankara expressing BKV VP1 (rMVA-BKV VP1) elicited functional CTL populations recognizing the sequences LLMWEAVTV (amino acids residues 108-116, BKV VP1p108) and AITEVECFL (residues 44-52, BKV VP1p44) and cross-reactive to the previously described JC virus VP1 homologs. Flow-based analyses of PBMC from a panel of thirty healthy HLA-A02 human volunteers indicated that the majority of these subjects harbored functional CTL populations recognizing the BKV epitopes and cross-reactive with the JCV homologs. CTL recognizing the JCV VP1p100 and JCV VP1p36 epitopes have previously been associated with prolonged survival in progressive multifocal leukoencephalopathy patients. These findings suggest that infection with BKV or JCV could potentially induce cross-protective T-cell immunity against diseases associated with these viruses.
在人类多瘤病毒BK病毒的VP1多肽中已鉴定出两个HLA - A02限制性表位,该病毒与肾移植患者的多瘤病毒相关性肾病有关。用表达BKV VP1的重组改良安卡拉痘苗病毒(rMVA - BKV VP1)免疫转基因小鼠,可引发功能性CTL群体,这些群体可识别序列LLMWEAVTV(氨基酸残基108 - 116,BKV VP1p108)和AITEVECFL(残基44 - 52,BKV VP1p44),并与先前描述的JC病毒VP1同源物发生交叉反应。对30名健康的HLA - A02人类志愿者的外周血单核细胞进行基于流式细胞术的分析表明,这些受试者中的大多数都含有可识别BKV表位并与JCV同源物发生交叉反应的功能性CTL群体。先前已发现,识别JCV VP1p100和JCV VP1p36表位的CTL与进行性多灶性白质脑病患者的长期存活有关。这些发现表明,感染BKV或JCV可能会潜在地诱导针对与这些病毒相关疾病的交叉保护性T细胞免疫。