BASIS OF DETERMINANT RECOGNITION BY THE IMMUNE SYSTEM

该项目汇集了一组研究人员， 免疫系统识别决定簇的分子和细胞起源 系统 该计划将利用核心设施的可用性， 用于肽合成和表征。 该研究将接近 在两个层面上的决定因素识别问题。 在程序I中，博士 威尔逊将继续进行流感血凝素的结构分析 (HA)一种抗原，它将作为所有抗原的共同特征。 他还将分析相互作用中固有的结构约束 HA决定簇（肽）与单克隆抗体结合位点之间 抗体的 决定性认知的基础是另一个层次， 体液和细胞反应的测定，将是常见的 其余五个项目的目标。 在计划II中，Lerner博士将 在肽水平上分析流感HA的识别， 这些研究有助于识别B型肝炎抗原。 这些研究 将讨论地形与线性决定因素在 生物学相关蛋白的免疫原性。 的基础 决定性的承认和不承认将在程序中解决 Klinman博士的第三章，使用不成熟（环境幼稚）和 成熟B细胞与代表自身蛋白决定簇的肽结合。 在 此外，克林曼博士还将研究环境的作用， 识别外源抗原的B细胞库的选择 仅在自身MHC同种异体抗原的情况下。 T的测定 识别MHC同种异体抗原本身和外来抗原的细胞库 在MHC同种异体抗原的背景下，抗原将是主要的关注点， 方案四至六。 在计划IV中，Chiller博士将研究 巨噬细胞Ia抗原提呈中的阳性和阴性选择 MHC限制性辅助性T细胞。 在第五计划中，谢尔曼博士将 研究H-2的“构象”决定因素在两种情况下的作用 溶细胞性T淋巴细胞对同种异体抗原和外来抗原的识别 （CTL）。 发展中国家积极选择的潜在作用 贝文博士将在项目VI中对CTL的环境进行研究。 通过 最大限度地使用共同的抗原和肽， 代表HA和H-2，协作互动， 培养应该大大加强这些方法中的每一个。

This Program Project brings together a group of investigators in a study of the molecular and cellular origins of determinant recognition by the immune system. The program will capitalize on the availability of a core facility for peptide synthesis and characterization. The research will approach the question of determinant recognition at two levels. In Program I, Dr. Wilson will continue the structural analysis of influenza hemagglutinin (HA), an antigen which will serve as a common denominator throughout all. He will also analyze the structural constraints inherent in the interaction between HA determinants, (peptides), and the combining site of monoclonal antibodies. The basis of determinant recognition of another level, that of the determination of humoral and cellular responses, will be the common purpose of the remaining five programs. In Program II, Dr. Lerner will analyze the recognition of the influenza HA at the peptide level and extend these studies to the recognition of hepatitis B antigens. These studies will address the role of topographic vs. linear determinants in the immunogenicity of biologically relevant proteins. The basis for determinant recognition and non-recognition will be addressed in Program III by Dr. Klinman, using responses of immature (environmentally naive) and mature B cells to peptides representative of self protein determinants. In addition, Dr. Klinman will also investigate the role of environmental selection on the repertoire of B cells which recognize foreign antigens only in the context of self MHC alloantigens. The determination of the T cell repertoire that recognizes MHC alloantigens per se and foreign antigens in the context of MHC alloantigens will be the major preoccupation of Programs IV-VI. In Program IV, Dr. Chiller will investigate th role of macrophage Ia antigen presentation in the positive and negative selection of MHC restricted helper T cells. In Program V, Dr. Sherman will investigate the role of "conformational" determinants of H-2 in both alloantigen and foreign antigen recognition by cytolytic T lymphocytes (CTL). The potential role of positive selection by the developing environment of CTL will be investigated in Program VI by Dr. Bevan. By maximizing the use of common antigens and peptides such as those representative of HA and H-2, the collaborative interactions which are fostered should greatly enhance each of these approaches.