CELLULAR AND MOLECULAR STUDIES OF HLA RECOGNITION

HLA 识别的细胞和分子研究

• 批准号: 3191344
• 负责人: ALAN MICHAEL KRENSKY
• 金额: $ 9.95万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3191344
• 关键词: T lymphocyte; antibody receptor; antiidiotype antibody; binding proteins; cell mediated cytotoxicity; cell mediated lymphocytolysis test; cellular immunity; clone cells; cytolysis; histocompatibility; histocompatibility antigens; immunotherapy; lymphoma; major histocompatibility complex; monoclonal antibody; neoplastic cell culture for noncancer research; peptides

The interaction of lympocytes with HLA molecules is a crucial event in immunobiology. We have recently shown that peptides corresponding to short linear sequences of HLA molicules can specifically inhibit cytolytic T lymphocyte (CTL) mediated cytolysis. This finding has important biologic and clinical significance. Biolobically, this finding suggests that the allogeneic response is a special case of nominal antigen recognition. That is, it appears that in some cases allogeneic HLA is seen as degraded peptides (or fragments) in the context of whole HLA. Clinically, this information is fundamental to the design of both inhibitory and/or stimulatory immunotherapy. Not only can peptides be used to modulate CTL effector function, but they may also be used diagnostically to define T cell clones of a particular specificity. Peptides may be altered in a variety of ways depending upon their ultimate purpose. The studies proposed here are designed to define the mechanism and biologic significance of peptide binding and inhibition. Specifically, we propose to: 1) define the molecular basis of inhibition of cytolysis by peptides, 2) use these peptides to investigate the mechanism of allogeneic recognition, 3) develop a panel of anti-clonotypic antibodies recognizing the T cell receptor from a series of HLA-A2 specific CTL, and 4) investigate the receptors. These studies will prove relevant to the immunobiology diagnosis, and therapy of cancer, transplant rejection, and autoimmune diseases.

淋巴细胞与HLA分子的相互作用是关键事件 在免疫生物学中。 我们最近表明肽 对应于hla molicules的短线性序列可以 特别抑制胞质T淋巴细胞（CTL）介导的 细胞解析。 这一发现具有重要的生物学和临床 意义。 从生物气上讲，这一发现表明 同种异体反应是名义抗原的特殊情况 认出。 也就是说，在某些情况下，同种异体HLA 在整个上下文中被视为降解的肽（或碎片） HLA。 临床上，此信息是设计的基础 抑制性和/或刺激性免疫疗法。 不仅可以 肽用于调节CTL效应子功能，但它们可能 也可以诊断用于定义特定的T细胞克隆 特异性。 肽可以通过多种方式改变 取决于他们的最终目的。 这里提出的研究 旨在定义的机制和生物学意义 肽结合和抑制。 具体而言，我们建议：1）定义的分子基础 通过肽抑制胞解，2）使用这些肽 研究同种异体识别的机制，3）发展 识别T细胞受体的抗粘液型抗体面板 从一系列HLA-A2特异性CTL中，4）研究 受体。 这些研究将证明与免疫生物学有关 癌症，移植排斥和治疗的诊断和治疗 自身免疫性疾病。