The recent findings that many more class I genes may be present within the major histocompatibility complex (MHC) than previously thought, and the emerging evidence that many of these genes encode tissue differentiation antigens, some of which may function in cell recognition outside the immune system, make it appropriate to look more intently at differentiation antigens, some of which may function in cell recognition outside the immune system, make it appropriate to look more intently at differentiation antigens encoded by the MHC. Among these differentiation antigens are highly polymorphic erythroid cell antigens encoded by the chicken MHC. These enigmatic antigens, the B-G antigens, have formed the basis of MHC typing in chickens from the time that the chicken MHC or B system of histocompatibility was first identified. We have purified and analyzed the B-G antigen from the one haplotype, B21, and have found evidence that B-G antigens may be unusual variants of MHC class I molecules. I propose to determine the molecular structure of the B-G 21 antigen in order to better understand the similarities and differences which exist between these polymorphic differentiation antigens and class I transplantation antigens. Microsequencing, tryptic peptide mapping and gene sequencing will be used to determine the structure of the B-G 21 antigen. Genomic and cDNA libraries will be prepared from which the B-G21 antigen gene will be cloned. The B21 class I gene(s) will also be isolated using murine class I gene probes and the sequence of this gene used in the comparative analysis of B-G21. These two genes will be mapped with respect to each other. The low frequency of recombination between them indicates they are closer to each other than many elements within the murine MHC. The basis of the polymorphism of the B-G antigens will be examined using suitable recombinant DNA probes derived from the cloned B-G21 gene. These data will help us to understand the organization and evolution of the MHC.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI021736-03
Application #
3132027
Study Section
Immunobiology Study Section (IMB)
Project Start
1985-02-01
Project End
1988-12-31
Budget Start
1987-02-01
Budget End
1988-12-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
City of Hope National Medical Center
Department
Type
DUNS #
City
Duarte
State
CA
Country
United States
Zip Code
91010
Miller, M M; Goto, R M; Taylor Jr, R L et al. (1996) Assignment of Rfp-Y to the chicken major histocompatibility complex/NOR microchromosome and evidence for high-frequency recombination associated with the nucleolar organizer region. Proc Natl Acad Sci U S A 93:3958-62
Jarvi, S I; Goto, R M; Briles, W E et al. (1996) Characterization of Mhc genes in a multigenerational family of ring-necked pheasants. Immunogenetics 43:125-35
Miller, M M; Goto, R; Bernot, A et al. (1994) Two Mhc class I and two Mhc class II genes map to the chicken Rfp-Y system outside the B complex. Proc Natl Acad Sci U S A 91:4397-401
Uni, Z; Pratt, W D; Miller, M M et al. (1994) Syngeneic lysis of reticuloendotheliosis virus-transformed cell lines transfected with Marek's disease virus genes by virus-specific cytotoxic T cells. Vet Immunol Immunopathol 44:57-69
Briles, W E; Goto, R M; Auffray, C et al. (1993) A polymorphic system related to but genetically independent of the chicken major histocompatibility complex. Immunogenetics 37:408-14
Miller, M M; Goto, R; Miyada, C G et al. (1992) Restriction fragment polymorphisms at the chicken anion transporter (band 3) locus. Anim Genet 23:290
Miller, M M; Goto, R; Young, S et al. (1991) Immunoglobulin variable-region-like domains of diverse sequence within the major histocompatibility complex of the chicken. Proc Natl Acad Sci U S A 88:4377-81
Miller, M M; Goto, R; Young, S et al. (1990) Antigens similar to major histocompatibility complex B-G are expressed in the intestinal epithelium in the chicken. Immunogenetics 32:45-50
Goto, R; Miyada, C G; Young, S et al. (1988) Isolation of a cDNA clone from the B-G subregion of the chicken histocompatibility (B) complex. Immunogenetics 27:102-9
Miller, M M; Goto, R; Briles, W E (1988) Biochemical confirmation of recombination within the B-G subregion of the chicken major histocompatibility complex. Immunogenetics 27:127-32

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