REGULATION OF IA GENE EXPRESSION

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Our research will include studying the tissue distribution of murine Ia gene expression by analyzing the presence of Ia-specific messenger RNAs in tissues and cell lines. We will use DNA probes derived from four cloned Ia genes, A-alpha, A-beta, E-alpha, and E-beta, in combination with three sensitive RNA assays, dot blots, Northern blots, and S1 nuclease mapping, to critically evaluate the tissues capable of Ia gene expression as well as their capacity for Ia gene induction. S1 nuclease mapping will aIso be used to determine if there is any alternative processing of Ia mRNA. Our investigstion will determine the ability of nonbone marrow-derived cells to express Ia genes by producing radiation chimeras. The characteristics of Ia gene induction in both tissues and cell lines including macrophages, dendritic cells, and T cells will be evaluated using known inducing agents including gamma interferon. We intend to critically test a recent hypothesis that Ia antigens are induced in grafted tissue on cells other than "passenger leukocytes" as a consequence of the allograft reaction. Finally, we will study the mechanism of Ia gene induction by transfecting cloned Ia genes into different cell types and selecting for inducible expression. (MB)