CD8 Mediated Apoptosis During T Cell Development

T 细胞发育过程中 CD8 介导的细胞凋亡

• 批准号: 6869103
• 负责人: TERRY A POTTER
• 金额: $ 19.9万
• 依托单位: NATIONAL JEWISH HEALTH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6869103
• 关键词: CD8 molecule; MHC class I antigen; T cell receptor; T lymphocyte; antigen presentation; antigen presenting cell; apoptosis; cell population study; developmental immunology; laboratory mouse; phorbols; tissue /cell culture

DESCRIPTION (provided by applicant): During the interaction of T cells with antigen presenting cells (APCs), receptors and intracellular proteins translocate into the contact region known as the Immunological Synapse (IS). In the first Aim we will examine whether CD8 behaves as a coreceptor within the immunological synapse, for the activation of peripheral T cells. In the other component of this proposal we shall follow up on our recent observation that cross-linking of CD8, but not CD4, with antibodies or MHC class I molecules, results in rapid apoptosis of CD4+CD8+ (DP) thymocytes. We have identified the thymocytes that are susceptible to this CD8 mediated apoptosis as an early DP population that expresses low levels of CD2 and CD5 and is CD69-. Treatment with the phorbol ester, PMA, or antibodies to CD3, prevents this induction of apoptosis. We hypothesize that ligation of CD8 by MHC class I molecules in the absence of TCR engagement leads to the death of a subpopulation of early DP thymocytes. Furthermore, our system may provide a model for thymocytes that fail positive selection and are said to undergo "death by neglect". In this proposal we shall further characterize the induction of apoptosis in DP thymocytes by CD8 antibodies and MHC class I molecules according to 3 specific aims: (i) to determine the biochemical events leading to the CD8 mediated death of DP thymocytes; (ii) to determine the mechanism by which treatment with PMA, or engagement of the TCR, prevents CD8 mediated death in DP thymocytes; (iii) to determine whether CD8 mediated death functions under physiological conditions.

描述（由申请人提供）：在T细胞与抗原呈递细胞（apc）相互作用期间，受体和细胞内蛋白转运到称为免疫突触（IS）的接触区域。在第一个目标中，我们将研究CD8是否作为免疫突触内的辅助受体，用于激活外周T细胞。