CHARACTERIZATION OF HIV-1-SPECIFIC T HELPER CELL CLONES

描述(改编自申请)：应聘者目前 参加了他的临床和研究奖学金的第二年 麻省总医院。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 哥伦比亚大学，并在杜克大学完成了他的医学实习 大学。这位候选人渴望成为一名基础科学研究人员 在一家主要的医疗中心，主要的研究重点得到了 临床责任。大部分时间将花在研究上。这个 拟议的研究培训方案所处的环境 完成将提供一个支持性的氛围和充足的机会 正式的学习和协作，并将为候选人准备 独立的调查生涯。 这项研究旨在描述HIV-1的性质和功能 来自急性和慢性粒细胞白血病患者的特异性T辅助细胞克隆 长期非进展性感染和治疗后慢性感染 接种疫苗。工作的重点将集中在确定广度， T辅助细胞对急性和慢性非霍奇金淋巴瘤的特异性和独特性 长期非进行性HIV-1感染，使用细胞和分子方法 技巧。接触独特的HIV-1感染者队列 接受有组织的治疗中断将为 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CD4+淋巴细胞 确诊为急性HIV-1血清转换疾病的人，长期 非进行性感染，以及接受治疗性疫苗接种的人。这个 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、良好的表位特异性、人类白细胞抗原限制性和细胞毒性 潜力。特定T细胞克隆的命运将在急性 使用寡核苷酸探针跟踪单个T细胞克隆和感染 与有效免疫反应的发展相关，无论是在 治疗和随后的治疗中断。要获得的知识 关于CD4+T淋巴细胞的产生和功能可能会进一步 了解HIV免疫致病机制并洞察其潜力 疫苗开发和免疫治疗方法。

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.