DEVELOPMENT OF HLA-B7 SUPERTYPE-BINDING HIV CTL VACCINES

描述：（改编自研究者摘要） 有证据表明CD 8细胞毒性T淋巴细胞（CTL）在保护性免疫中起作用。 应对艾滋病毒。CTL识别短病毒肽表位， 与病毒感染细胞上的HLA I类分子的关联。不幸的是， 由于人类群体中存在许多等位基因，每个个体 倾向于向CD 8淋巴细胞“呈递”不同的病毒肽。这项建议 聚焦于一组称为HLA-B7，B55，B53，B35， B54、B56、B67和B78。HLA B-7超型覆盖了约49%的 这些等位基因倾向于结合相同的病毒肽表位。一 一组HIV CCTL表位，在HIV感染者中定义， 与一个或多个B7超型等位基因的关联已经被选择用于 在这里学习。(1)这组表位与不同的B7 将检查超类型。最多将有四个不同的表位 根据它们将a结合到多个B7超型的能力来选择 等位基因进行进一步研究。(2)选择的HLA-B7超型结合HIV 将检查表位在体外诱导CTL应答的能力， 来自表达不同B7的未感染供体的人CD 8 T淋巴细胞 超型等位基因针对最佳B7产生的CTL 将检查（2）中的超型限制性HIV CTL表位的（3）它们的 识别病毒感染细胞中内源性产生的表位的能力 并抑制体外HIV感染，以及（4）它们识别 病毒变体表位。总的来说，这些研究将努力定义一个 与多种B7超型免疫原性的HIV CTL表位 等位基因，并诱导其他HIV毒株的交叉识别。因此这些 研究将为纳入交叉反应性B7 超型限制性HIV CTL表位在新疫苗方法中的应用

DESCRIPTION: (Adapted from the investigator's abstract) Several lines of evidence implicate CD8 cytotoxic T lymphocytes (CTL) in protective immune responses against HIV. CTLs recognize short viral peptide epitopes in association with HLA class I molecules on virus-infected cells. Unfortunately, due to the presence of many alleles in the human population, each individual tends to "present" different viral peptides to CD8 lymphocytes. This proposal focuses on a group of HLA-B class alleles termed the HLA-B7, B55, B53, B35, B54, B56, B67, and B78. The HLA B-7 supertype covers approximately 49% of the population, and those alleles tend to bind identical viral peptide epitopes. A group of HIV CCTL epitopes that were defined in HIV-infected individuals in association with one or more of the B7 supertype alleles has been selected for study here. (1) The binding of this group of epitopes to different B7 supertypes will be examined. A maximum of four distinct epitopes will be selected on the basis of their ability to bind a to multiple B7 supertype alleles for further study. (2) The selected HLA-B7 supertype-binding HIV epitopes will be examined for their ability to elicit CTL responses in vitro in human CD8 T lymphocytes from uninfected donors expressing different B7 supertype alleles. The CTLs generated against the optimal B7 supertype-restricted HIV CTL epitopes in (2) will be examined for (3) their ability to recognize endogenously generated epitopes in virus-infected cells and inhibit HIV infection in vitro, and for (4) their ability to recognize viral variant epitopes. Collectively, these studies will strive to define one or more HIV CTL epitopes that are immunogenic with multiple B7 supertype alleles and that induce cross-recognition of other HIV strains. Thus, these studies will provide the foundation for the inclusion of cross reactive, B7 supertype-restricted HIV CTL epitopes in new vaccine approaches.