FUNCTIONAL INTERACTIONS OF I AND H-2K/D IR GENES

I 和 H-2K/D IR 基因的功能相互作用

• 批准号: 3126536
• 负责人: Peter Johnson Wettstein
• 金额: $ 16.39万
• 依托单位: WISTAR INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-08-01 至 1987-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3126536
• 关键词: T lymphocyte; gene expression; genetic mapping; histocompatibility antigens; histocompatibility gene; immune complex; immunoglobulin genes; immunoregulation; linkage mapping; major histocompatibility complex; serology /serodiagnosis

Genes mapping in the H-2K/D and I regions of the major histocompatibility complex (H-2) of mice play a pivotal role in regulating the interactions of lymphocytes in the immune response. The linkage of H-2K/D and I region analogs has been maintained throughout mammalian evolution suggesting that H-2K/D and I region genes interact to regulate immune responses which are selectively advantageous. I have observed that the T cell response to single non-H-2 histocompatibility (H) alloantigens is regulated by antigen-specific immune response (IR) genes mapping in both I and H-2K/D regions. I propose to conduct a comprehensive genetic and immunological analysis of the functional interactions of these two Ir gene systems. The Ir genes which control recipient responsiveness in vivo and in vitro will be characterized by determining their H antigen specificity, minimum number, and intra-H-2 map positions. Similarly, the Ir genes which regulate the presentation or immunogenicity of non-H-2 antigens will be mapped and their H antigen-specificity determined. The possible preferential association of single H antigen-specific fast responsiveness and high immunogenicity alleles at I and H-2K/D loci in specific H-2 haplotypes will be investigated; this investigation is aimed at revealing I:H-2K/D linkage disequilibrium in mice. The cellular level of expression of the genes controlling recipient responsiveness will be determined by Ly phenotyping T cells responding to non-H-2 H antigens. Similarly, the identity of cells presenting non-H-2 H antigens will be determined. The suspected role of I and H-2K/D Ir genes in antigen-specific regulation of the interactions between non-H-2 H antigen-specific T cells and H antigen-positive stimulator and target cells will be confirmed. Techniques will be employed to demostrate that non-H-2 H antigens associated with Ir gene products, which have variable affinity for H antigens, to form immunogenic complexes on the cell membrane. Complementary experiments will be conducted to determine the specificity of the T cell receptor(s) for non-H-2 antigen and "self" H-2 complex molecules by serological characterization of the respective T cell receptor idiotypes.

主要组织相容性H-2K/D和I区基因定位 复合物（H-2）在调节小鼠的相互作用中起着关键作用。 淋巴细胞参与免疫反应。 H-2K/D和I区类似物的连接 在哺乳动物的进化过程中一直保持着，这表明H-2K/D和I 区域基因相互作用以调节免疫应答， 优势的 我观察到T细胞对单个非H-2的反应 组织相容性（H）同种异体抗原受抗原特异性免疫调节， 在I和H-2K/D区域中定位IR反应（IR）基因。 我提议 一个全面的基因和免疫分析的功能 这两个基因系统的相互作用。 控制受体的IR基因 体内和体外的反应性将通过测定其H 抗原特异性、最小数目和H-2图谱内位置。 同样地， 调节非H-2的呈递或免疫原性的Ir基因 将绘制抗原并确定它们的H抗原特异性。 的 单个H抗原特异性快 特异性免疫反应性和高免疫原性等位基因在I和H-2K/D基因座 H-2单倍型将被调查;这项调查的目的是揭示 I：小鼠中的H-2K/D连锁不平衡。 细胞水平表达的 控制受体反应性的基因将由Ly决定 对非H-2 H抗原应答的T细胞进行表型分析。 同样，身份 将确定呈递非H-2 H抗原的细胞的量。 可疑角色 I和H-2K/D Ir基因在抗原特异性调节相互作用中的作用 非H-2 H抗原特异性T细胞和H抗原阳性刺激物之间的关系， 将确认目标细胞。 技术将被用来证明， 与Ir基因产物相关的非H-2 H抗原，其具有可变的 对H抗原的亲和力，以在细胞膜上形成免疫原性复合物。 将进行补充实验以确定 非H-2抗原和“自身”H-2复合物分子的T细胞受体， 相应T细胞受体独特型的血清学表征。