BASIS OF DETERMINANT RECOGNITION BY THE IMMUNE SYSTEM

这个项目汇集了一组调查人员， 主要兴趣是免疫系统对决定簇的识别 但他的个人专长从蛋白质分析 结构与B细胞和T细胞刺激参数的关系。 一个重要的新 该计划的倡议是由项目四，其中博士。 帕特森正在提出一个独立的项目，以继续她的研究（从 项目III）关于B细胞识别的结构修饰 和细胞色素c的确定肽的T细胞。 添加NMR 赖特博士为该计划提供的研究不仅有助于这些 研究，但将是中心的建议博士勒纳（项目二）谁 计划进一步完善表明抗肽抗体 优先结合蛋白质，如果肽来源于 具有高分子迁移率的蛋白质。 这些研究加上博士的研究。 Wilson（项目I），其中PR 8的三维结构 将分析血凝素（HA）和相关肽， 它们与单克隆抗体的相互作用，将提供结构上的 该计划中项目的基础重点是 免疫细胞选择对决定簇识别的贡献。 为 例如，项目VI中的谢尔曼博士将跟进她早期的预测 CTL特异性是基于识别新的符合的， 自身MHC抗原 除了研究H-2b突变体，她还将 还分析了转染细胞和转基因细胞中表达的抗原， 小鼠 以类似的方式，第五项目的奇勒博士将研究辅助性T细胞 外显子改组的I类MHC基因和外源基因的细胞识别 抗原 不承认自我决定因素的机制是 Klinman博士将继续研究诱导和维持 项目III和项目VII的贝文博士。 项目七将侧重于 “否决”细胞在自我识别的监视和维持中的作用 而项目III将继续评估自身MHC在塑造 B细胞库，并与谢尔曼和奇勒博士合作， 将尝试构建表达流感HA的转基因小鼠， “伪自体抗原”。

This program project brought together a group of investigators whose primary interests concerned determinant recognition by the immune system but whose individual expertise ranged from the analysis of protein structure to the parameters of B cell and T cell stimulation. A major new initiative in this program is represented by project IV in which Dr. Paterson is proposing an independent project to continue her studies (from project III) on the structural requisites for the recognition by B cells and T cells of defined peptides of cytochrome c. The addition of NMR studies provided by Dr. Wright to this program will aid not only these studies but will be central to the proposal of Dr. Lerner (project II) who plans to further refine findings that indicate that anti-peptide antibodies preferentially bind to proteins, if the peptide is derived from a region of the protein with high molecular mobility. These studies plus those of Dr. Wilson (project I) wherein the three-dimensional structure of the PR8 hemagglutinin (HA) and related peptides will be analyzed with respect to their interactions with monoclonal antibodies, will provide structural underpinnings for the projects in this program that focus on the contributions of immunocyte selection to determinant recognition. For example, Dr. Sherman in project VI will follow up on her early predictions that CTL specificity is predicated on the recognition of novel conforms of self MHC antigens. In addition to her studies of H-2b mutants she will also analyse antigens expressed on transfected cells and in transgenic mice. In a similar fashion, Dr. Chiller in project V will study helper T cell recognition of exon-shuffled class I MHC genes and of foreign antigens. The mechanism by which non-recognition of self determinants is induced and maintained will continue to be studied by Dr. Klinman in project III and Dr. Bevan in project VII. Project VII will focus on the role of "veto" cells in surveillance and maintenance of self recognition whereas project III will continue to assess the role of self MHC in shaping the B cell repertoire and, in collaboration with Drs. Sherman and Chiller, will attempt to construct transgenic mice expressing the influenza HA as a "pseudo-self antigen".