BK VIRUS IMMUNITY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 多瘤病毒BK(BKV)的重新激活会导致肾移植(KTX)受者的多瘤病毒肾病(PVN)，并可能导致移植肾的丢失。我们已经鉴定了BKV主要衣壳蛋白VP1、VP1(P44)和VP1(P108)的两个HLA-A*0201限制性九个氨基酸的细胞毒性T淋巴细胞(CTL)表位。使用四聚体染色分析，我们发现这些表位在10例(VP1(P44))和5例(VP1(P108))健康个体中被CTL识别，而在10例经活检证实为PVN的KTX受者中，这两个表位都能引起10例CTL反应，尽管水平不同。体外刺激后，在大多数健康人中，针对VP1(P44)的CTL比针对VP1(P108)的CTL更丰富，而在患有PVN的KTX受者中则相反，这表明在BKV活动性感染的背景下，表位免疫优势发生了变化。在伴有PVN的KTX受者中，强烈的CTL应答与血和尿中BK病毒载量的降低和抗BKV抗体滴度的降低有关，而低或未检测到的CTL应答与病毒持久性和抗BKV抗体滴度的高水平有关。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，并在控制患有PVN的KTX受者的BKV中发挥重要作用。有趣的是，BKV的CTL表位与最近报道的其他人类多瘤病毒JC(JCV)、JCV VP1(P36)和VP1(P100)的CTL表位具有惊人的同源性。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在功能上对这两种密切相关的病毒是有效的。

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.