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

主要组织相容性H-2K/D区和I区的基因定位 小鼠复合体(H-2)在调节细胞间相互作用中起关键作用 免疫反应中的淋巴细胞。H-2K/D和I区类似物的连锁 在整个哺乳动物进化过程中一直保持着，这表明H-2K/D和I 区域基因相互作用来调节免疫反应，选择性地 有利的。我观察到T细胞对单一非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 反应(IR)基因定位于I和H-2K/D区。我建议进行 功能性遗传病的遗传学和免疫学综合分析 这两个ir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它们的H 抗原特异性、最小数目和H-2内MAP位置。同样， 调节非H-2病毒提呈或免疫原性的ir基因 将绘制抗原图谱，并确定其H抗原特异性。这个 单一H抗原特异性FAST的可能优先关联性 特异的I和H-2K/D基因座的反应性和高免疫原性等位基因 将调查H-2单倍型；这项调查的目的是揭示 I：H-2K/D连锁不平衡。在细胞水平上表达的 控制接受者反应的基因将由Ly决定 对非H-2H抗原作出反应的T细胞的表型。同样，身份也是如此 将确定呈现非H-2H抗原的细胞的数量。可疑的角色 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-2H抗原特异性T细胞与H抗原阳性刺激因子之间的关系 将确认目标单元格。我们将使用各种技术来演示 与ir基因产物相关的非H-2H抗原，具有可变性 与H抗原的亲和力，在细胞膜上形成免疫原复合体。 将进行补充实验，以确定该病毒的特异性 T细胞受体(S)对非H-2抗原和“自身”H-2复合分子的作用 各T细胞受体独特型的血清学特征。

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.