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

MHC 结合、SIV 衍生、CTL 和 HTL 表位

• 批准号: 7716392
• 负责人: David I Watkins
• 金额: $ 16.38万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-23 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7716392
• 关键词: Alleles; Animals; Arginine; Binding; CD4 Positive T Lymphocytes; Cell Line; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Epitopes; Funding; Gene Frequency; Grant; HIV; HIV vaccine; Helper-Inducer T-Lymphocyte; Human; Immune response; Immunogenetics; Infection; Institution; Leucine; MHC Class I Genes; Macaca; Macaca mulatta; Maps; Peptides; Positioning Attribute; Publishing; Reagent; Research; Research Personnel; Resources; SIV; Services; Source; Staining method; Stains; Testing; United States National Institutes of Health; Work; cohort; cytokine; cytotoxic; enzyme linked immunospot assay; novel; preference; virology

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. 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. The preliminary binding motif of Mamu-B*08 has been determined and shown to contain a dominant preference for arginine at the P2 anchor position along with a dominant preference for leucine at the P9 C-terminus. Currently, a detailed peptide binding motif is being defined. Nine novel SIV derived peptide epitopes restricted by Mamu-B*08 have been identified, while three other regions are currently being mapped to minimal optimal epitopes. These have been mapped by a combination of intracellular cytokine staining and ELISPOT in responder cell lines or PBMC's derived from animals that are elite controllers (and some progressors) of a highly pathogenic SIVmac239 infection. MHC class I tetramers have been successfully produced and verified for 9 minimal optimal Mamu-B*08 epitopes (eight of which have been published). Three other MHC class I tetramers are under development. It is important to note that MHC typing data shows that Mamu-B*08 is over represented among a cohort of rhesus macaques that control SIVmac239 infection. While the overall frequency of this allele in a cohort of 196 WNPRC macaques infected with SIVmac239 is 5.6% (11 of 196), the frequency of this allele among elite controllers is 37.5% (6 of 16). Furthermore, the binding motif of the Mamu-B*08 allele is similar to that of HLA-B*27, an allele in humans associated with control of HIV. Additional testing is currently ongoing to investigate how close the peptide binding motif is between these two alleles. This research used WNPRC Immunogenetics & Virology Services and Animal Services.

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。 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。 已经确定了Mamu-B*08的初步结合基序，并显示其在P2锚位置处含有对精氨酸的显性偏好，沿着在P9 C末端处含有对亮氨酸的显性偏好。目前，正在定义详细的肽结合基序。已经鉴定了9个新的SIV衍生的受Mamu-B*08限制的肽表位，而另外3个区域目前正在定位于最小最佳表位。这些已经通过细胞内细胞因子染色和ELISPOT的组合在应答细胞系或PBMC中作图，所述应答细胞系或PBMC来源于作为高致病性SIVmac 239感染的精英控制者（和一些进展者）的动物。已经成功地产生了MHC I类四聚体，并验证了9个最小最佳Mamu-B*08表位（其中8个已发表）。其他三种MHC I类四聚体正在开发中。重要的是要注意，MHC分型数据显示Mamu-B*08在控制SIVmac 239感染的恒河猴群中过度代表。虽然在感染SIVmac 239的196只WNPRC猕猴的队列中该等位基因的总频率为5.6%（11/196），但在精英控制者中该等位基因的频率为37.5%（6/16）。 此外，Mamu-B*08等位基因的结合基序类似于HLA-B*27的结合基序，HLA-B*27是人类中与HIV控制相关的等位基因。目前正在进行其他测试，以研究这两个等位基因之间的肽结合基序有多接近。这项研究使用了WNPRC免疫遗传学和病毒学服务和动物服务。