BAA APPLICATION OF HLA DATA TO DEVELOP & IMPROVE VACCINE

有效的免疫反应需要针对自身主要组织相容性复合体(MHC)I类和II类分子呈递的抗原的T淋巴细胞的发展。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，它们的检测还不准确和繁琐，需要广泛的组织培养程序。已经开发出新的试剂，由四个相同的MHC分子组成，每个分子代表一个确定的抗原肽。试剂被荧光标记，以实现对通过其特定抗原受体分子结合试剂的T细胞的直接检测。以前的研究已经建立了I类MHC分子与细胞毒性T细胞结合的方法，但基于II类MHC分子的检测辅助T淋巴细胞的试剂还不太发达。该合同将专注于II类MHC多肽四聚体的开发和利用，以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-多肽复合体，以优化试剂；b)展示试剂在临床样本中检测人类T细胞的能力；以及c)将检测与功能T细胞分析相结合，以增加获得的信息。由于辅助T细胞是几乎所有免疫反应的中心，这项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。

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.