This application is for continued support of our efforts to characterize, at a molecular level, the class I gene family of the human major histocompatibility complex (MHC). The human MHC is designated the HLA complex. In addition to maintaining the transplantation barrier between individuals, molecules encoded by the MHC have a central role in regulating the immune response. MHC class I molecules are recognized together with foreign antigens at the cell surface of target cells by the receptor on cytotoxic T lymphocytes. Multiple genetic loci within the human MHC encode class I proteins. The experiments described in this proposal will focus on two interesting aspects of HLA class I molecular genetics. The molecular characterization of the non-A,B,C class I genes and their expression will be undertaken to provide insights into their function. A particularly intriguing question concerns a possible functional relationship between one or all of the HLA non-A,B,C class I molecules and cells expressing the gamma/delta receptor molecule. The second group of experiments will identify and characterize factors important in the regulation of HLA class I gene transcription. Regulation of class I gene expression is an important component in determining whether a cell can interact with T cells in a functionally significant manner.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI018124-10
Application #
3127700
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1989-09-30
Project End
1994-07-31
Budget Start
1990-08-01
Budget End
1991-07-31
Support Year
10
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Schmidt, C M; Garrett, E; Orr, H T (1997) Cytotoxic T lymphocyte recognition of HLA-G in mice. Hum Immunol 55:127-39
Schmidt, C M; Orr, H T (1995) HLA-G transgenic mice: a model for studying expression and function at the maternal/fetal interface. Immunol Rev 147:53-65
Schmidt, C M; Chen, H L; Chiu, I et al. (1995) Temporal and spatial expression of HLA-G messenger RNA in extraembryonic tissues of transgenic mice. J Immunol 155:619-29
Schmidt, C M; Ehlenfeldt, R G; Athanasiou, M C et al. (1993) Extraembryonic expression of the human MHC class I gene HLA-G in transgenic mice. Evidence for a positive regulatory region located 1 kilobase 5' to the start site of transcription. J Immunol 151:2633-45
Yelavarthi, K K; Schmidt, C M; Ehlenfeldt, R G et al. (1993) Cellular distribution of HLA-G mRNA in transgenic mouse placentas. J Immunol 151:3638-45
Schmidt, C M; Orr, H T (1991) A physical linkage map of HLA-A, -G, -7.5p, and -F. Hum Immunol 31:180-5
Killeen, A A; Sane, K S; Orr, H T (1991) Molecular and endocrine characterization of a mutation involving a recombination between the steroid 21-hydroxylase functional gene and pseudogene. J Steroid Biochem Mol Biol 38:677-86
Wei, X H; Orr, H T (1990) Differential expression of HLA-E, HLA-F, and HLA-G transcripts in human tissue. Hum Immunol 29:131-42
Koller, B H; Geraghty, D E; DeMars, R et al. (1989) Chromosomal organization of the human major histocompatibility complex class I gene family. J Exp Med 169:469-80
Mizuno, S; Trapani, J A; Koller, B H et al. (1988) Isolation and nucleotide sequence of a cDNA clone encoding a novel HLA class I gene. J Immunol 140:4024-30

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