MHC-BOUND, SIV-DERIVED, CTL AND HTL EPITOPES

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， 因此可以在其他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。 目的：为了开发艾滋病毒疫苗，我们将确定细胞毒性和辅助性T细胞的其他表位，并利用这些信息开发用于以下免疫反应的独特试剂。 HLA-B27-和-B57-阳性HIV感染的人长期以来与HIV复制的控制相关，这意味着CD 8 + T细胞应答有助于控制病毒复制。 以类似的方式，50%的Mamu-B*08阳性印度恒河猴控制SIVmac 239复制，并成为慢性期病毒血症低于1,000 vRNA拷贝/ml的精英控制者。 有趣的是，Mamu-B*08限制性SIV衍生表位似乎与人类HLA-B*2705的肽结合谱相匹配。 因此，我们定义了Mamu-B*08的详细肽结合基序，并研究了猕猴和人MHC I类分子之间的结合相似性。 对一组近900个肽的分析显示，尽管Mamu-B*08和HLA-B*2705之间存在实质性的序列差异，但这两种MHC I类分子的肽结合库共享显著程度的重叠。 对Mamu-B*08肽结合基序的详细了解使我们能够鉴定出另外六种针对Gag、Vpr和Env中表位的新型Mamu-B*08限制性SIV特异性CD 8 + T细胞免疫应答。 所有13个Mamu-B*08限制性表位在第2位初级锚处含有R，并且10个还在N末端处具有R或K。 这样的二元肽不易于细胞降解。 这项工作突出了Mamu-B*08阳性SIV感染的印度恒河猴作为研究免疫缺陷病毒复制精英控制模型的相关性。 Mamu-B*08和HLA-B*2705的肽结合基序和库的显著相似性表明，由MHC I类分子结合的肽的性质可能在控制免疫缺陷病毒复制中起重要作用。这项研究使用了WNPRC免疫遗传学和病毒学服务和动物服务。

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 work on developing a vaccine for HIV, we will identify additional epitopes for cytotoxic and helper T cells and use this information to develop unique reagents for following immune responses. HLA-B27- and -B57-positive HIV-infected humans have long been associated with control of HIV replication, implying that CD8+ T cell responses contribute to control of viral replication. In a similar fashion, fifty percent of Mamu-B*08-positive Indian rhesus macaques control SIVmac239 replication and become elite controllers with chronic phase viremia below 1,000 vRNA copies/ml. Interestingly, Mamu-B*08-restricted SIV-derived epitopes appeared to match the peptide binding profile for HLA-B*2705 in humans. We, therefore, defined a detailed peptide-binding motif for Mamu-B*08 and investigated binding similarities between the macaque and human MHC class I molecules. Analysis of a panel of almost 900 peptides revealed that despite substantial sequence differences between Mamu-B*08 and HLA-B*2705, the peptide-binding repertoires of these two MHC class I molecules share a remarkable degree of overlap. Detailed knowledge of the Mamu-B*08 peptide-binding motif enabled us to identify six additional novel Mamu-B*08-restricted SIV-specific CD8+ T cell immune responses directed against epitopes in Gag, Vpr, and Env. All 13 Mamu-B*08-restricted epitopes contain an R at the position 2 primary anchor, and 10 also possess either R or K at the N-terminus. Such dibasic peptides are less prone to cellular degradation. This work highlights the relevance of the Mamu-B*08-positive SIV-infected Indian rhesus macaque as a model to examine elite control of immunodeficiency virus replication. The remarkable similarity of the peptide-binding motifs and repertoires for Mamu-B*08 and HLA-B*2705 suggests that the nature of the peptide bound by the MHC class I molecule may play an important role in control of immunodeficiency virus replication. This research used WNPRC Immunogenetics & Virology Services and Animal Services.