BASIS OF DETERMINANT RECOGNITION BY THE IMMUNE SYSTEM

该计划项目汇集了一组调查人员，他们的 主要关注免疫系统对决定簇的识别 但他们的个人专长从蛋白质分析到 结构对B细胞和T细胞刺激的参数。一项重大的新技术 本方案中的倡议由项目IV代表，在该项目中，Dr。 帕特森正在提议一个独立的项目来继续她的学习(来自 项目三)关于B细胞识别的结构条件 和确定的细胞色素c.多肽的T细胞。核磁共振的添加 赖特博士为该项目提供的研究将不仅有助于 研究，但将是勒纳博士提案的核心(项目二)，世卫组织 计划进一步完善表明抗肽抗体 优先与蛋白质结合，如果多肽来自于 具有高分子流动性的蛋白质。这些研究加上Dr。 威尔逊(项目I)，其中PR8的三维结构 血凝素(HA)和相关的多肽将分析关于 它们与单抗的相互作用，将提供结构 本计划中的项目的基础是 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的特异性是基于对新构象的识别 自身MHC抗原。除了她对H-2b突变的研究外，她还将 也分析在转基因细胞和转基因细胞上表达的抗原 老鼠。以类似的方式，奇勒博士在项目V中将研究助手T 外显子改组的I类MHC基因和外源基因的细胞识别 抗原。自我决定因素不被认可的机制是 诱导和维持将继续由Klinman博士在 项目三和Bevan博士在项目七中。项目七将侧重于 “否决权”细胞在自我认知监控和维持中的作用 鉴于项目III将继续评估自身MHC在形成过程中的作用 B细胞谱系，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 “伪自身抗原”。

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".