Abstract

Hybrid resistance is the prevention of proliferation of grafts of H-2 homozygous normal or neoplastic hemopoietic cells by F1 hybrid mice heterozygous at H-2. This observation goes against the laws of transplantation genetics, which state that histocompatibility antigens are inherited codominantly. The determinants for the major hybrid or hemopoietic histocompatibility (Hh) antigens map at H-2D.
The aims here are to determine if genes in the trans or cis configuration with Hh regulate expression so as to determine immunogenicity of donor cells and presence or absence of hybrid resistance in F1 hybrid hosts. The possibility of allogeneic inhibition, i.e., recognition of host alloantigens by the donor cells to initiate the response, will be investigated. Finally, the mechanism of tolerance induction to Hh antigens will be explored. The potential importance of this work relates to autoimmunity and tumor immune surveillance, since the parent and the F1 hybrid share the structural gene for the same Hh antigen. (SR)

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA036921-03
Application #
3174576
Study Section
(SSS)
Project Start
1984-03-01
Project End
1987-02-28
Budget Start
1986-03-01
Budget End
1987-02-28
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of Texas Sw Medical Center Dallas
Department
Type
Schools of Medicine
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390

  Publications

George, T C; Mason, L H; Ortaldo, J R et al. (1999) Positive recognition of MHC class I molecules by the Ly49D receptor of murine NK cells. J Immunol 162:2035-43
George, T C; Ortaldo, J R; Lemieux, S et al. (1999) Tolerance and alloreactivity of the Ly49D subset of murine NK cells. J Immunol 163:1859-67
Liu, J; Sentman, C L; Kumar, V et al. (1997) Murine marrow coexpressing H2-Dsp2 and H2-Db on host natural killer cell rejection. Transplantation 63:444-9
Manoussaka, M; Georgiou, A; Rossiter, B et al. (1997) Phenotypic and functional characterization of long-lived NK cell lines of different maturational status obtained from mouse fetal liver. J Immunol 158:112-9
George, T; Yu, Y Y; Liu, J et al. (1997) Allorecognition by murine natural killer cells: lysis of T-lymphoblasts and rejection of bone-marrow grafts. Immunol Rev 155:29-40
Kumar, V; George, T; Yu, Y Y et al. (1997) Role of murine NK cells and their receptors in hybrid resistance. Curr Opin Immunol 9:52-6
Moore, T A; Bennett, M; Kumar, V (1996) Murine natural killer cell differentiation: past, present, and future. Immunol Res 15:151-62
Yu, Y Y; George, T; Dorfman, J R et al. (1996) The role of Ly49A and 5E6(Ly49C) molecules in hybrid resistance mediated by murine natural killer cells against normal T cell blasts. Immunity 4:67-76
Liu, J; Yu, Y Y; Lindahl, K F et al. (1996) Allorecognition by murine natural killer cells: studies with bone marrow transplants and lysis of T lymphoblasts. Chem Immunol 64:164-80
Bennett, M; D'Orazio, T; Kumar, V et al. (1995) Bone marrow cell transplants involving donors and hosts with haplotypes derived from spretus mice. Transplantation 59:1452-9

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