Antigens encoded or controlled by the Qa/Tla region are restricted to cells of the hematopoietic lineage and serve as phenotypic markers of distinct lymphocyte subpopulations. Recent reports, however, suggest that Qa/Tla encoded antigens may also be selectively expressed in other cell types. Although no functions have been ascribed to these differentiation antigens, several of the Qa/Tla antigens do have evolutionary and structural features in common with the class I major transplantation antigens which are integral components in the regulation of immune responses. Seven antigens and their respective loci have been identified in the Qa/Tla complex; other as yet undefined class I loci exist in this region based on DNA hybridization experiments. This proposal is concerned with the biochemical analysis of the TL, Qa-1 and Qa-2/4 antigens and the definition and elucidation of other novel alloantigens encoded within the Qa/Tla region. The role of carbohydrate in the chemical structure, cell surface expression and alloantigenicity will be examined using tunicamycin and various glycosidases. The nature and extent of structural polymorphism that exists among the four defined Qa-1 allelic products will be studied using 2-dimensional gel electrophoresis and comparative peptide mapping. We plan to analyze the structural relationships among the Qa-1 antigens, the H-2Kf, -Df antigens, and a 60-75K protein encoded by mice of the H-2f, Qa-1d genotype. We have recently reported that the TL antigen, thought to be a cell surface marker restricted to thymocytes, is expressed by both mitogen and alloantigen activated peripheral T lymphocytes. A major focus of this proposal is the further biochemical and flow cytometric investigation of TL expressed on different lymphoid subpopulations and by different Tla alleles. Experiments addressing the mechanisms of induction/derepression of TL expression and possible insights into functions of TL in immune responses are also described. The biochemical structure of the Qa-4 alloantigen and its relationship to the Qa-2 antigen will be examined using a monoclonal anti-Qa-4 antibody. Finally, we intend to continue our monoclonal antibody program to generate monoclonal reagents to the previously defined and to novel Qa/Tla gene products. These proposed experiments should aid in unraveling the genetic and structural complexity of the Qa/Tla region.
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