NON-H-2 HISTOCOMPATIBILITY GENES AND ENCODED ANTIGENS

外源基因编码的组织相容性(H)抗原 主要组织相容性复合体组成了一个强大的 组织移植成功的障碍。虽然这个家庭 非H-2H抗原在小鼠中起到了重要的作用 研究T细胞反应调节的模型系统， 对它们的起源和功能几乎一无所知。 抗原。这一持续的节目旨在澄清 多个和单一H抗原的应答机制。 我们最近发现，H抗原是由 逆转录病毒和肿瘤病毒的种系整合。这个 建议的研究计划是一种多方面的方法 了解T细胞的机制和调节 对H抗原的反应及其成员的鉴定 重要的家庭。第一批实验的目的是揭示 优先的体外T细胞应答的基础 免疫优势抗原及其与T细胞反应的相关性 活着。潜在的作用：(1)优先呈现优势 H-2K/D分子的抗原，(2)亲和力的差异和 T细胞表面IL-2受体的数量 优势抗原，以及(2)不同类别的优势抗原 对于辅助T细胞和细胞溶解T细胞将进行研究。T细胞 将分析对单个H抗原的反应以确定(1) H-2K分子离散区域在H抗原中的作用 Ir基因状态的表示和确定，(2)影响 H抗原特异性T细胞使用的T细胞受体V基因 抗原特异性和H-2限制性内切酶，以及(3)两者的关系 体内和体外T细胞反应机制之间的关系。 这些研究将得到克隆和 非H-2H基因的鉴定。观察到SV40 T抗原被视为H抗原在转基因小鼠中将被 通过确定不同启动子和 作为H抗原表达的侧翼区域。这个 一种新的乳腺肿瘤病毒与H突变株的相关性研究 将通过克隆这种逆转录病毒来确认抗原，以评估其 编码这种H抗原的能力。浅谈外衣与外衣的关系 颜色和H基因突变将被延长以确认毛皮 颜色突变逆转会导致H抗原的丢失。最后， 逆转录病毒载体将被用作插入诱变剂 失活单个H基因；整合的克隆 逆转录病毒将促进H基因的首次克隆 COSMID图书馆。

Histocompatibility (H) antigens encoded by genes mapping outside of the major histocompatibility complex comprise a formidable barrier to successful tissue transplantation. Although the family of non-H-2 H antigens in the mouse has served as an important model system for studying the regulation of the T cell response, virtually nothing is known of the origins and functions of these antigens. This continuing program has been aimed at elucidating the mechanisms of responses to multiple and single H antigens. We have recently discovered that H antigens are generated by germline integration of retroviruses and tumor viruses. The proposed research plan is a multi-faceted approach to understanding the mechanisms and regulation of the T cell response to H antigens and the identification of members of this important family. The first experiments are aimed at revealing the basis for the preferential, in vitro T cell response to immunodominant antigens and its relevance to T cell responses in vivo. Potential roles for (1) preferential presentation of dominant antigens by H-2K/D molecules, (2) differences in affinity and number of IL-2 receptors on T cells specific for dominant and dominated antigens, and (2) different classes of dominant antigens for helper and cytolytic T cells will be investigated. The T cell response to single H antigens will be analyzed to determine (1) the role of discrete regions of H-2K molecules in H antigen presentation and determination of Ir gene status, (2) the effects of T cell receptor V genes used by H antigen-specific T cells on antigen specificity and H-2 restriction, and (3) the relationship between the mechanisms of in vivo and in vitro T cell responses. These studies will be complemented by the cloning and identification of non-H-2 H genes. The observation that the SV40 T-antigen is seen as an H antigen in transgenic mice will be extended by determining the effects of different promoters and flanking regions on its expression as an H antigen. The association between a new mammary tumor virus and a mutant H antigen will be confirmed by cloning this retrovirus to assess its ability to encode this H antigen. The relationship between coat color and H gene mutations will be extended to confirm that coat color mutant reversions lead to the loss of H antigens. Finally, retroviral vectors will be employed as insertional mutagens to inactivate a single H gene; the cloning of the integrated retrovirus will facilitate the first cloning of an H gene from a cosmid library.