BK VIRUS IMMUNITY

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 多瘤病毒BK（BKV）的再活化导致肾移植（KTx）受者的多瘤病毒肾病（PVN），并可能导致肾移植物丢失。我们已经确定了BKV主要衣壳蛋白VP 1的两个HLA-A*0201限制性9个氨基酸的细胞毒性T淋巴细胞（CTL）表位，VP 1（p44）和VP 1（p108）。使用四聚体染色分析，我们发现这些表位在10个HLA-A*0201+健康个体中的8个（VP 1（p44））和10个HLA-A*0201+健康个体中的5个（VP 1（p108））中被CTL识别，而这两个表位在10个KTx接受者中的10个中引起CTL应答，尽管在不同的水平上。在体外刺激与各自的肽，针对VP 1（p44）的CTL更丰富的比对VP 1（p108）在大多数健康的人，而匡威的是真实的KTx收件人与PVN，表明表位免疫优势的转移，在设置活动BKV感染。在PVN的KTx受者中，强烈的CTL应答似乎与血液和尿液中BK病毒载量降低以及抗BKV抗体滴度低相关，而低或检测不到的CTL应答与病毒持续存在和高抗BKV抗体滴度相关。这些结果表明，这种细胞免疫反应存在于大多数BKV血清阳性的健康个体中，并在PVN KTx接受者的BKV遏制中发挥重要作用。有趣的是，BKV CTL表位与最近描述的其他人多瘤病毒JC（JCV）的CTL表位JCV VP 1（p36）和VP 1（p100）具有惊人的同源性。在BKV和相应的JCV特异性CTL之间存在高度的表位交叉识别，这表明相同的细胞群体在功能上有效对抗这两种密切相关的病毒。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Reactivation of the polyomavirus BK (BKV) causes polyomavirus nephropathy (PVN) in kidney transplant (KTx) recipients and may lead to loss of the renal allograft. We have identified two HLA-A*0201-restricted nine-amino-acid cytotoxic T lymphocyte (CTL) epitopes of the BKV major capsid protein VP1, VP1(p44), and VP1(p108). Using tetramer staining assays, we showed that these epitopes were recognized by CTLs in 8 of 10 (VP1(p44)) and 5 of 10 (VP1(p108)) HLA-A*0201+ healthy individuals, while both epitopes elicited a CTL response in 10 of 10 KTx recipients with biopsy-proven PVN, although at variable levels. After in vitro stimulation with the respective peptides, CTLs directed against VP1(p44) were more abundant than against VP1(p108) in most healthy individuals, while the converse was true in KTx recipients with PVN, suggesting a shift in epitope immunodominance in the setting of active BKV infection. A strong CTL response in KTx recipients with PVN appeared to be associated with decreased BK viral load in blood and urine and low anti-BKV antibody titers, while a low or undetectable CTL response correlated with viral persistence and high anti-BKV antibody titers. These results suggest that this cellular immune response is present in most BKV-seropositive healthy individuals and plays an important role in the containment of BKV in KTx recipients with PVN. Interestingly, the BKV CTL epitopes bear striking homology with the recently described CTL epitopes of the other human polyomavirus JC (JCV), JCV VP1(p36) and VP1(p100). A high degree of epitope cross-recognition was present between BKV and corresponding JCV-specific CTLs, which indicates that the same population of cells is functionally effective against these two closely related viruses.