CORRELATES OF ELITE CONTROL OF SIV

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。 目的：了解猕猴精英控制者(ECs)的“控制相关因素”。 “保护的相关性”，即保护接种疫苗的人免受艾滋病毒感染的免疫反应，是未知的。正因为如此，人们对研究“精英控制者”(ECs)产生了浓厚的兴趣，“精英控制者”是一种罕见的自发控制艾滋病毒复制的人。在过去的几年里，我们聚集了一群精英控制器猕猴，它们在几个重要方面与人类ECs相似。这个项目旨在了解这些猕猴ECs中的“控制相关因素”。 此前，我们发现猕猴群体中的精英控制与特定的MHC-I类(MHC-I)等位基因MAMU-B*17和MAMU-B*08的表达有关。引人注目的是，我们队列中的所有猕猴精英控制者都至少表达这些等位基因中的一个。这些蛋白质向CD8+T细胞呈递来自SIV蛋白的多肽“表位”，“标记”受感染的细胞进行破坏。由于MAMU-B*17和B*08在细胞免疫反应中发挥作用，因此我们推测，表达这些蛋白的动物产生的特异性CD8+T细胞反应使它们有可能成为ECs。因此，该项目探索了CD8+T细胞反应，特别是那些被Mamu-B*17和B*08“限制”的反应，对猕猴内皮细胞中SIV的免疫抑制作用。 并不是所有Mamu-B*17或B*08阳性的猕猴在感染SIV时都会成为ECs。为了了解成功和不成功反应的区别，我们因此全面比较了EC和进展者猕猴对SIV的细胞免疫反应，这些猕猴都表达Mamu-B*17。引人注目的是，我们发现免疫反应的强度或ECs和进展者中识别的病毒表位的数量都没有明显的差异(1)。目前的研究旨在确定特定的CD8+T细胞反应是否与Mamu-B*17阳性的ECs抵抗不同病毒的重新攻击的能力相关。 这项研究使用了WNPRC动物服务、遗传学服务和免疫学和病毒学服务。

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. Objective: To understand the "correlates of control" in macaque elite controllers (ECs). The "correlates of protection," i.e., the immune responses which will protect vaccinated individuals against HIV infection, are unknown. Because of this, there is intense interest in studying "elite controllers" (ECs), rare individuals who spontaneously control HIV replication. Over the past few years we have assembled a cohort of elite controller macaques that resemble human ECs in several important respects. This project is aimed at understanding the "correlates of control" in these macaque ECs. Previously we showed that elite control in our macaque cohort was associated with expression of particular MHC class I (MHC-I) alleles, Mamu-B*17 and Mamu-B*08. Strikingly, all macaque elite controllers in our cohort express at least one of these alleles. These proteins present peptide "epitopes" derived from SIV proteins to CD8+ T cells, "flagging" infected cells for destruction. Since Mamu-B*17 and B*08 play a role in the cellular immune response, we therefore hypothesized that the specific CD8+ T cell responses made by animals expressing these proteins made it possible for them to become ECs. This project has therefore probed the contribution of CD8+ T cell responses, particularly those "restricted" by Mamu-B*17 and B*08, to immune containment of SIV in macaque ECs. Not all Mamu-B*17- or B*08-positive macaques become ECs when they are infected with SIV. To understand what distinguishes successful and unsuccessful responses, we therefore comprehensively compared the cellular immune responses to SIV in EC and progressor macaques that all expressed Mamu-B*17. Strikingly, we found no apparent differences in either the strength of immune responses or number of viral epitopes recognized in ECs and progressors (1). Current studies are aimed at determining whether particular CD8+ T cell responses are correlated with the ability of Mamu-B*17-positive ECs to resist rechallenge with divergent viruses. This research used WNPRC Animal Services, Genetics Services, and Immunology & Virology Services.