CHARACTERIZATION OF HIV-1-SPECIFIC T HELPER CELL CLONES

HIV-1 特异性辅助细胞克隆的表征

• 批准号: 6212816
• 负责人: Philip J. Norris
• 金额: $ 11.38万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6212816
• 关键词: HIV infections; MHC class II antigen; cellular immunity; clinical research; clone cells; cytokine; epitope mapping; helper T lymphocyte; human immunodeficiency virus 1; human subject; protein biosynthesis

DESCRIPTION (adapted from the application): The candidate is currently enrolled in his second year of a clinical and research fellowship at the Massachusetts General Hospital. He holds degrees in bioengineering and molecular biology from the University of California, Berkeley, an M.D. from Columbia University, and completed his residency in medicine at Duke University. The candidate aspires to a career as a basic science researcher at a major medical center, with a dominant research focus complimented by clinical responsibilities. The bulk of time would be spent in research. The environment in which the proposed research training program will be accomplished will provide a supportive atmosphere with ample opportunity for formal learning and collaboration, and will prepare the candidate for an independent investigative career. The research is aimed at characterizing the nature and function of HIV-1 specific T-helper cell clones derived from individuals with acute and long-term nonprogressive infection, and chronic infection after therapeutic vaccination. The focus of the work will center on identifying the breadth, specificity and unique attributes of the T-helper cell response to acute and long-term nonprogressive HIV-1 infection, using both cellular and molecular techniques. Access to the unique cohorts of HIV- 1-infected persons undergoing structured treatment interruptions will provide novel insights into the role of T helper cells in control of viremia. HIV-1-specific CD4+ lymphocytes will be isolated and cloned from individuals identified with acute HIV-1 seroconversion illness, those with long-term nonprogressive infection, and those treated with therapeutic vaccination. The clones will be analyzed in detail, monitoring their cytokine and chemokine production, fine epitope specificity, HLA restriction, and cytotoxic potential. The fate of specific T cell clones will be followed in acute infection using oligonucleotide probes to track individual T cell clones and correlated with the development of an effective immune response, both during treatment and following treatment interruption. The knowledge to be gained regarding the generation and function of CD4+ T lymphocytes may further the understanding of HIV immunopathogenesis and shed insight into potential vaccine development and immunotherapeutic approaches.

描述（改编自应用程序）：候选人目前 在他的临床和研究奖学金的第二年， 马萨诸塞州综合医院。 他拥有生物工程学位， 来自加州大学伯克利分校的分子生物学博士，从 哥伦比亚大学，并在杜克大学完成了医学实习 大学 这位候选人渴望成为一名基础科学研究人员 在一个主要的医疗中心，与一个主导的研究重点称赞， 临床责任。 大部分时间将用于研究。 的 环境中，拟议的研究培训计划将是 完成将提供一个支持性的气氛与充分的机会， 正式的学习和合作，并将准备候选人 独立的调查生涯。 该研究旨在表征HIV-1的性质和功能 特异性T辅助细胞克隆来源于急性和慢性淋巴细胞白血病患者， 长期非进展性感染和治疗后慢性感染 预防针 工作的重点将集中在确定广度， T辅助细胞对急性和慢性炎症反应的特异性和独特属性， 长期非进展性HIV-1感染，使用细胞和分子 技术. 接触艾滋病毒1型感染者的独特群体 接受结构化治疗中断将提供新的见解， 辅助性T细胞在控制病毒血症中的作用。 将从个体中分离和克隆HIV-1特异性CD 4+淋巴细胞 确定患有急性HIV-1血清转化疾病的人， 非进行性感染和治疗性疫苗接种。 的 将对克隆进行详细分析，监测它们的细胞因子和趋化因子 生产、精细表位特异性、HLA限制性和细胞毒性 潜力 将在急性淋巴细胞白血病中跟踪特定T细胞克隆的命运。 使用寡核苷酸探针追踪单个T细胞克隆的感染， 与有效免疫反应的发展相关， 治疗和治疗中断后。 所获得知识 关于CD 4 + T淋巴细胞的产生和功能， 了解艾滋病毒的免疫发病机制，并深入了解潜在的 疫苗开发和免疫方法。