HUMAN TL (HTL) REGION IN THE HLA LINKAGE GROUP

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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.