GENETIC REGULATION OF LYMPHOID DIFFERENTIATION ANTIGENS

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The overall objective of this project is to elucidate the mechanisms by which HLA class II genes are regulated. The specific aims for this project period are: 1) to continue and complete development of a method of cloning transactive transcriptional factors, retroviral transactivation, which is not based on protein-DNA binding and is not dependent on mRNA abundance; 2) to identify and clone genes for transcription factors, particularly non-DNA binding transcription factors, which regulate expression of HLA class II genes and other genes important in the immune response; 3) to study transcriptional regulation of HLA class II genes using the cloned transactive factor genes; and 4) to continue investigation of post-translational mechanisms which effect HLA class II gene expression and function. Two general approaches will be used for cloning class II transcriptional factors, retroviral transactivation and complementation of class II transactive factor mutants. We expect that studies using cloned transactive regulatory genes will lead to a better understanding of the way that class II genes are regulated. Because the magnitude of T cell responses is dependent on levels of class II expression of antigen presenting cells, these studies in turn should help to elucidate an important determinant of T cell function. In addition we hope to elucidate the nature of the normal functioning of the genes mutated in the various forms of the Bare Lymphocyte Syndrome.