BASIS OF DETERMINANT RECOGNITION BY THE IMMUNE SYSTEM

这四个项目有两个相互关联的总体主题。首先， Bevan和Klinman实验室(项目一和项目二)将解决 T、B细胞受体谱系表达的发育基础。自.以来 成熟T细胞受体的谱系主要由胸腺决定 环境选择，贝文实验室将评估对 它们在野生型存在下发育的T细胞的良好特异性 VS突变的MHC分子。新生儿和成人B细胞的克隆发育 细胞亚集将由Klinman在分子水平上进行寻址 将使用PCR技术生成V区文库的实验室 来自发育中的B系细胞克隆的基因组DNA的序列。 Bevan实验室在研究T细胞的三方相互作用时 受体、多肽和MHC分子，克林曼实验室 评估B细胞谱系多样性，两人都将参加第二次 总主题、受体-抗原相互作用的结构及其 与剧目多样性的关系。盖佐夫实验室将继续 它对抗病毒Fab片段结构的分析很有前景 细胞色素c抗体和与抗原结合的相同Fab。这些 研究应该提供关于所做接触的关键信息 抗体和抗原之间的关系以及相互作用的灵活性 分子。这一信息是《勒纳》的背景 实验室，该实验室建议继续其开创性的努力来预测 并找到能够催化化学物质的抗体结合部位结构 反应。 在过去的几年里，主要的调查人员受益于 很大程度上来自通过该计划提供的共同核心设施 项目和赠款所促进的智力互动。这个 目前的建议旨在促进这些措施的继续 互动。

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.