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 S?1? nuclease mapping, to critically evaluate the tissues capable of Ia gene expression as well as their capacity for Ia gene induction. S?1? 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)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA039070-03
Application #
3177836
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1984-07-01
Project End
1987-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Kentucky
Department
Type
Schools of Medicine
DUNS #
832127323
City
Lexington
State
KY
Country
United States
Zip Code
40506
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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