BAA-APPLICATION OF HLA DATA TO DEVELOP & IMPROVE VACCINE

BAA-HLA 数据的开发应用

• 批准号: 6360186
• 负责人: lawrence stern
• 金额: $ 32.37万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6360186
• 关键词: MHC class II antigen; T lymphocyte; fluorescent dye /probe; immunologic assay /test; leukocyte activation /transformation; stainings; technology /technique development; tissue /cell culture; vaccine development

Effective immune responses require the development of T lymphocytes specific for antigens presented by self major histocompatibility complex (MHC) class I and class II molecules. Many basic and clinical studies require the detection and enumeration of antigen- specific T lymphocytes, but until recently their detection was inaccurate and cumbersome, requiring extensive tissue culture procedures. New reagents have been developed, comprised of four identical MHC molecules, each presenting a defined antigenic peptide. The reagent is fluorescently labeled to enable the direct detection of T cells that bind the reagent by their specific antigen receptor molecules. Previous research has established the approach for class I MHC molecules that bind to cytotoxic T cells, but reagents based upon class II MHC molecules, which would detect helper T lymphocytes, are less well-developed. This contract will focus on the development and utilization of class II MHC-peptide tetramers to detect and study antigen specific T cells. Studies will include: a) testing various forms of class II MHC-peptide complexes to optimize the reagents, b) demonstrate the reagents~ ability to detect human T cells in clinical samples and c) combine detection with functional T cell assays to increase the information obtained. Because helper T cells are central to virtually all immune responses, this technology is applicable to studies in many areas, including basic immune mechanisms, infectious diseases, vaccination, autoimmunity, transplant rejection, and tumor therapy.

有效的免疫应答需要对自身主要组织相容性复合体（MHC）I类和II类分子呈递的抗原具有特异性的T淋巴细胞的发育。 许多基础和临床研究需要检测和计数抗原特异性T淋巴细胞，但直到最近，它们的检测是不准确和繁琐的，需要大量的组织培养程序。新试剂已被开发出来，由四个相同的MHC分子组成，每个分子都呈现一个确定的抗原肽。该试剂被荧光标记以能够直接检测通过其特异性抗原受体分子结合试剂的T细胞。 先前的研究已经建立了与细胞毒性T细胞结合的I类MHC分子的方法，但是基于II类MHC分子的试剂，其将检测辅助T淋巴细胞，还没有得到很好的开发。 该合同将重点开发和利用II类MHC-肽四聚体来检测和研究抗原特异性T细胞。研究将包括：a）测试各种形式的II类MHC-肽复合物以优化试剂，B）证明试剂检测临床样品中的人T细胞的能力和c）将联合收割机检测与功能性T细胞测定结合以增加获得的信息。 由于辅助性T细胞是几乎所有免疫反应的核心，因此该技术适用于许多领域的研究，包括基本免疫机制，传染病，疫苗接种，自身免疫，移植排斥和肿瘤治疗。