Functional TCR analysis of SIV specific CTL

SIV特异性CTL的功能TCR分析

• 批准号: 7058616
• 负责人: Marcelo J Kuroda
• 金额: $ 30.53万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7058616
• 关键词: MHC class II antigen; Macaca mulatta; T cell receptor; cytotoxic T lymphocyte; flow cytometry; immunization; microorganism immunology; plasmids; polymerase chain reaction; protein structure function; receptor expression; simian immunodeficiency virus; vector vaccine; virus antigen

DESCRIPTION (provided by applicant): Although affinity maturation is a well-documented characteristic of B cell responses, recent studies indicate that T cells may also undergo an affinity maturation process. It is well accepted that antigen-specific T cells generated during primary immune responses are usually broadly polyclonal. However, repeated re-exposure to the same antigen gives rise to T cell populations with a more restricted T cell receptor (TCR) repertoire and higher antigen affinities. TCR repertoires of virus-specific CTL have been extensively studied in the setting of HIV-1 infection. However, the functional TCR repertoire of CD8 + T cell responses specific for individual viral epitopes remains poorly characterized in infected, and especially in vaccinated individuals. To date, studies of the TCR repertoire of epitope-specific CTL using either the entire CD8 v T cell population or tetramer technology to isolate antigen-specific CTL from PBL of infected individuals has been restricted to analysis of the alpha or beta chain separately. These studies have provided limited information concerning the functional evolution of epitope-specific CD8 + T cells. In the studies described in this application, we will use novel soluble TCR tetramers to characterize the functional evolution of TCRs that recognize dominant and subdominant SIV-, CTL epitopes that arise during immunization. Specifically, we will 1. Determine the repertoire of the TCR alpha and beta chain pairs of SIV-specific CTL generated by DNA or recombinant adenovirus vaccination of Mamu-A*01+ rhesus monkeys 2. Compare the affinities of TCR that recognize SIV CTL epitopes using soluble TCR tetramer complexes 3. Assess the affinity maturation of the TCRs involved in SIV-specific T cell responses in a heterologous prime-boost vaccination strategy.

描述（由申请人提供）：尽管亲和成熟是B细胞反应的一个充分证明的特征，但最近的研究表明T细胞也可能经历亲和成熟过程。人们普遍认为，在原发性免疫反应中产生的抗原特异性T细胞通常是广泛的多克隆细胞。然而，反复暴露于同一抗原会导致T细胞群具有更有限的T细胞受体（TCR）库和更高的抗原亲和力。