The cellular and genetic mechanisms that control the expression of the murine Ia antigens will be studied in an effort to better understand the regulation of the immune response. Since Ia antigen expression can have a profound effect on the severity and type of immune response generated in normal and disease situations, understanding the mechanisms of regulation of Ia expression in different cell types is of central importance.
The specific aims of this proposal are 1) To investigate the intracellular pathways involved in Ia induction at the membrane, mRNA and transcriptional levels. This will involve comparison of different methods of Ia induction and evaluation of the roles of protein kinase C and cyclic AMP-mediated signal transduction pathways. 2) To further characterize a newly discovered mechanism of regulation of the E-beta gene, namely, a block in transcriptional elongation that is regulated by IFN-gamma. This will involve nuclear run-off analysis of transcription rates along the E-beta gene in different cell types. 3) Characterize the sequence involved in the transcriptional blockage by insertion into CAT vectors specifically designed to evaluate transcriptional termination sequences. 4) Evaluate the presence of sequence specific DNA binding proteins that may interact with the region involved in transcriptional blockage.
|Stuart, P M; Munn, R K; DeMoll, E et al. (1995) Characterization of human T-cell responses to Yersinia enterocolitica superantigen. Hum Immunol 43:269-75|
|Egan, R M; Brockman, J A; Omer, K W et al. (1994) Transcription of the murine class II Eb gene is regulated primarily at the level of transcriptional initiation. Cell Immunol 156:537-43|
|Stuart, P M; Egan, R M; Woodward, J G (1993) Characterization of MHC induction by Mycoplasma fermentans (incognitus strain). Cell Immunol 152:261-70|
|Cerosaletti, K M; Woodward, J G; Lord, E M et al. (1992) Two regions of the H-2 Dd promoter are responsive to dimethylsulfoxide in line 1 cells by a mechanism distinct from IFN-gamma. J Immunol 148:1212-21|
|Stuart, P M; Woodward, J G (1992) Yersinia enterocolitica produces superantigenic activity. J Immunol 148:225-33|
|Kern, M J; Woodward, J G (1991) The same CCAAT box-binding factor binds to the promoter of two coordinately regulated major histocompatibility complex class II genes. Mol Cell Biol 11:578-81|
|Stuart, P M; Yarchover, J L; Woodward, J G (1989) Negative trans-acting factors extinguish Ia expression in B cell-L 929 somatic cell hybrids. Cell Immunol 122:391-404|
|Kern, M J; Stuart, P M; Omer, K W et al. (1989) Evidence that IFN-gamma does not affect MHC class II gene expression at the post-transcriptional level in a mouse macrophage cell line. Immunogenetics 30:258-65|
|Woodward, J G; Omer, K W; Stuart, P M (1989) MHC class II transcription in different mouse cell types. Differential requirement for protein synthesis between B cells and macrophages. J Immunol 142:4062-9|
|Stuart, P M; Cassell, G H; Woodward, J G (1989) Induction of class II MHC antigen expression in macrophages by Mycoplasma species. J Immunol 142:3392-9|
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