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， 应答 该建议旨在从分子水平上定义， 诱导细胞相互作用的抗原要求 调节CTL反应。 从拟议的 该项目可能导致有效的临床干预手段，召唤 在自身免疫性疾病的情况下诱导特异性抑制， 器官或组织移植，以及特定的增强反应， 恶性肿瘤或病毒感染病例。 使用I类主要组织相容性复合体（MHC）的既往研究 抗原已允许证明Ly 1+，2，3-辅助因子和抑制因子 用于CTL应答的T细胞。 然而，直到最近， 为了精确地定义这些调节事件， 负责CTL应答的MHC抗原是完整的膜 蛋白质，因此难以操作。 为了定义 触发一个途径优先于另一个纯化途径的分子事件 将使用插入脂质体中的膜抗原。 纯化的H-2Kk和 I-A抗原，克隆的应答性T淋巴细胞，单克隆 抗原呈递细胞系和克隆的I-A基因将用于 解决这样的问题：是否识别相同形式的抗原 通过辅助细胞和抑制细胞（例如，天然的与APC修饰的或 构象决定簇）; MHC膜内和 胞质内结构域刺激反应; 抑制与帮助的激活; 抗原和Ia;以及Ia结构和功能相关性， 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.