BASIS OF DETERMINANT RECOGNITION BY THE IMMUNE SYSTEM

这四个项目有两个相互关联的总主题。一是 Bevan和Klinman实验室（项目I和II）将解决 T和B细胞受体库表达的发育基础。以来 成熟T细胞受体库主要由胸腺决定， 环境选择，贝文实验室将评估的影响， 它们在野生型存在下发育的T细胞的良好特异性 与突变型MHC分子相比。新生和成年B的克隆发育 细胞亚群将在分子水平上解决的克林曼 该实验室将使用PCR技术产生V区文库， 来自发育中的B谱系细胞克隆的基因组DNA的序列。 贝文实验室，在解决T细胞的三方相互作用， 受体，肽和MHC分子，以及克林曼实验室在 评估B细胞库的多样性，都将参与第二次 总的来说，受体-抗原相互作用的结构及其 与剧目多样性的关系。Getzoff实验室将继续 它的有前途的分析的结构的Fab片段的抗 细胞色素c抗体和与抗原复合的相同Fab。这些 研究应提供关于所进行的接触的重要信息， 抗体和抗原之间以及相互作用的灵活性 分子。这一信息作为背景的勒纳 该实验室建议继续其开创性的努力， 并找到能够催化化学反应的抗体结合位点结构， 反应. 在过去的几年里，主要的调查人员受益匪浅。 通过该计划提供的通用CORE设施 项目和赠款所促进的智力互动。的 目前的建议是为了促进这些继续 交互.

There are two overall themes interrelating the four projects. First, the Bevan and Klinman laboratories (projects I and II) will address the developmental basis of T and B cell receptor repertoire expression. Since the repertoire of mature T cell receptors is determined largely by thymic environmental selection, the Bevan laboratory will assess the impact on their fine specificity of T cells developing in the presence of wild type vs mutant MHC molecules. The clonal development of neonatal and adult B cell subsets will be addressed at the molecular level by the Klinman laboratory which will use PCR technology to generate libraries of V region sequences from the genomic DNA of developing B lineage cell clones. The Bevan laboratory, in addressing the tripartite interaction of T cell receptors, peptides, and MHC molecules, and the Klinman laboratory in assessing B cell repertoire diversity, will both participate in the second overall theme, the structure of receptor-antigen interaction and its relationship to repertoire diversity. The Getzoff laboratory will continue its promising analyses of the structure of an Fab fragment of anti cytochrome c antibody and the same Fab in complex with antigen. These studies should provide crucial information concerning the contacts made between antibodies and antigens and the flexibility of interacting molecules. This information serves as the backdrop for the Lerner laboratory, which proposes to continue its pioneering efforts to predict and find antibody combining site structures capable of catalyzing chemical reactions. During the past several years the principle investigators have profited greatly from the common CORE facility made available through this program project and the intellectual interactions the grant has fostered. The present proposal is intended to facilitate the continuation of these interactions.