This proposal is a continuation of our efforts to characterize, using molecular genetics, the class I gene family of the human major histocompatibility complex (MHC). In addition to maintaining the transplantation barrier between individuals, molecules encoded by the MHC have a central role in regulating the immune response. The class I loci constitute a multigene family whose hallmark is a high level of polymorphism. We will continue to focus our attention on the class I gene family of lymphoblastoid cell line (LCL) 721. LCL 721 was chosen because of the large number of HLA deletion mutants which have been derived from it by Dr. DeMars of the University of Wisconsin. These mutants have been used to map DNA fragments to the known HLA-A and -B alleles of LCL 721 (26). Two of these, HLA-A2 and -A1 will be cloned and sequenced as a beginning in understanding the molecular basis of HLA polymorphism. Our mapping studies have also identified class I-like sequences located telomeric to HLA-A2 (19), as an analogous position relative to the MHC as the murine QA-Tla genes. In order to ascertain the relationship between the human class I-like telomeric sequences and the murine Qa-Tla genes, we will obtain genomic clones of the telomeric segments. These will then be subjected to DNA sequencing and studies directed at determining if these sequences include expressed genes. An important aspect will be to determine the tissue distribution of any class I-like genes found to be expresses. Understanding the relationship to the murine Qa-Tla genes of the human class I-like DNA located telomerically to HLA should help to identify useful markers of human lymphocyte differentiation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI018124-07
Application #
3127698
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1981-08-01
Project End
1989-07-31
Budget Start
1987-08-01
Budget End
1988-07-31
Support Year
7
Fiscal Year
1987
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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