ANALYSIS OF IA MOLECULES IN THE IMMUNOREGULATION OF CTL

一系列复杂的细胞相互作用，包括辅助细胞和 抑制细胞途径，影响细胞免疫的产生 回应。这项提议旨在从分子水平上定义， 诱导细胞相互作用的抗原性要求 它调节CTL反应。从建议中获得的信息 项目可能导致有效的临床干预手段，传唤 在自身免疫性疾病病例中诱导特异性抑制 器官或组织移植，以及对 恶性肿瘤或病毒感染的病例。 以往使用I类主要组织相容性复合体(MHC)的研究 抗原允许Ly1，2，3-Helper和Inhibitor的展示 T细胞用于CTL反应。然而，直到最近，这一点一直很困难。 为了准确定义这些调控事件，因为抗原 负责CTL反应的MHC抗原，是完整的细胞膜 蛋白质，因此很难操纵。为了定义 分子事件触发前围栏中的一条通往另一条纯化的途径 将使用插入脂质体中的膜抗原。纯化的H-2Kk和 I-A抗原，克隆的反应T淋巴细胞，单克隆性 抗原提呈细胞系，以及克隆的I-A基因将被用于 解决下列问题：是否承认相同形式的抗原 由帮助者和抑制者细胞(例如，原生的与修改的APC或 构象决定因素)；膜内和膜内MHC的作用 刺激反应的胞质内结构域； 抑制与帮助的激活；两者之间的联系的性质 抗原和Ia；以及Ia结构和功能的相关性 生化分析以及重组DNA。

A complex series of cellular interactions, including both helper cell and suppressor cell pathways, influences the generation of cellular immune responses. This proposal is directed at defining, on a molecular level, the antigenic requirements for the induction of the cellular interactions which regulate the CTL response. The information gained from the proposed project may lead to means of efficient clinical intervention, summons the induction of specific suppression in cases of autoimmune disorders and organ or tissue transplants, and the specific enhancement of responses in cases of malignancies or viral infections. Previous studies using class I major histocompatibility complex (MHC) antigens have allowed the demonstration of Ly1+,2,3- helper and suppressor T cells for CTL responses. Until recently however, it has been difficult to precisely define these regulatory events because the antigens responsible for the CTL response, the MHC antigens, are integral membrane proteins and thus are difficult to manipulate. In order to define the molecular events triggering one pathway in prefence to the other purified membrane antigens inserted into liposomes will be used. Purified H-2Kk and I-A antigens, cloned responding T lymphocytes, monoclonal antigen-presenting cell lines, and cloned I-A genes will be utilized to address such issues as: whether the same forms of antigen are recognized by both helper and suppressor cells (e.g. native vs. APC modified or conformational determinants); the role of MHC intramembranous and intracytoplasmic domains for stimulation of responses; the kinetics of activation of suppression vs. help; the nature of the association between antigen and Ia; and Ia structure and function correlations using biochemical analysis as well as recombinant DNA.