HUMAN TL (HTL) REGION IN THE HLA LINKAGE GROUP

本提案的目的是检测和表征人类T （HT 1a）区基因产物被来自 多产妇女。 在过去两年中， 同种抗血清已经被表征。 一般来说，两组 分化同种抗原，这两个似乎是多态性基因 一组仅在胸腺细胞上表达，T 白血病细胞和淋巴母细胞样细胞系，暂命名为HTL （TL样），而另一组在活化的淋巴细胞上表达， 静息脾细胞和淋巴结细胞称为HT（Qa样）抗原。 两组同种异体抗原均与β 2-微球蛋白相关， 可能与HLA区域有关 实验旨在更好地定义 这些多态性同种异体抗原通过与 同种抗血清和利用单克隆抗体的生物化学方法。 将采用交叉吸收法研究血清学差异 HTL和HT基因产物之间的关系。 高分辨率等电聚焦 采用凝胶电泳和Western blot检测 生化结构和遗传多态性的推定 同种抗原 这些抗原将从放射性标记的细胞中获得， 使用同种抗血清和单克隆抗体的顺序免疫沉淀 来识别不同的β 2 m相关分子。 我们的具体目标将 是：a）确定HT和HTL基因产物是否含有Beta 2 m并 研究HTL和HT抗原之间的血清学差异。 B）学习 HLA和HTL基因产物簇之间的连锁不平衡， HLA基因分型家系HT决定簇分离分析 c）、 证明HT和HTL基因产物的结构多态性。 d）、 以产生针对HT和HTL决定簇的单克隆抗体。 我们的长期目标是确定基因和基因的精细结构 一种新的遗传系统的产物，可能相当于鼠T1 a 遗传系统 这些发现将有助于扩大我们对 MHC（HLA和非HLA）基因产物在免疫调节中的作用 以及提供用于同种异体移植的组织分型的新试剂。

The objectives of this proposal are to detect and characterize the human T (HT1a) region gene products recognized by alloantisera procured from multiparous women. During the last two years, significant number of alloantisera have been characterized. Generally, two groups of differentiation alloantigens, both of which appear to be polymorphic gene products, were recognized: One group is expressed only on thymocytes, T leukemic cells and lymphoblastoid cell lines which is tentatively named HTL (TL-like), while the other group is expressed on activated lymphocytes, resting spleen cells and lymph node cells named HT (Qa-like) antigens. Both groups of alloantigens are associated with Beta2-microglobulin and are probably linked to the HLA region. Experiments will aim to better define these polymorphic alloantigens by means of serological reactivity with alloantisera and by biochemical methods utilizing monoclonal antibodies. Cross-absorption will be used in order to study the serological differences between HTL and HT gene products. High resolution isoelectrofocusing (IEF) gel electrophoresis and Western blot will be used to detmonstrate biochemical structure and genetic polymorphism of the putative alloantigens. These antigens will be obtained from radiolabelled cells by sequential immunoprecipitation using alloantisera and monoclonal antibodies to recognize different Beta2m-associated molecules. Our specific aims will be: a) to determine if HT and HTL gene products contain Beta 2m and to study serological differences between HTL and HT antigens. b) To study linkage disequlibrium between HLA and clusters of HTL gene products and to study segregation analysis of HT determinants in HLA genotyped familes. c) To demonstrate structural polymorphism of the HT and HTL gene products. d) to produce monoclonal antibodies directed against HT and HTL determinants. Our long term objectives is to define the fine structure of gene and gene products of a new genetic system which may be equivalent to the murine T1a genetic system. Such findings will be useful to extend our knowledge of the role of MHC (HLA and non-HLA) gene products in the immune regulation and in providing new reagents for tissue typing for allotransplantation.