The long-term objective of this project is to understand the genetic mechanism(s) underlying the natural resistance to hemopoietic allografts. As an initial approach towards the stated objective, three specific aims are proposed: 1) to determine the location of the Hh-1 locus in the H-2-b and H-2-d chromosomes by determining restriction fragment length polymorphism (RFLP) in a panel of H-2S/D recombinant haplotypes, 2) to identify and isolate the Hh-1 genes, using human and murine probes for the H-2S/D interval and H-2-b and H-2-d cosmid libraries, and 3) to initiate the characterization of the genes thus identified. The proposed approach should provide new insight into the genetic mechanism underlying natural resistance and the recognition function of NK cells. In addition, these studies should help identify homologous genes in man, improve the prospect of clinical bone marrow transplantation, and possibly develop NK cell-mediated cancer immunotherapy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA052519-01A1
Application #
3197272
Study Section
Experimental Immunology Study Section (EI)
Project Start
1991-04-01
Project End
1994-03-31
Budget Start
1991-04-01
Budget End
1992-03-31
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
Name
State University of New York at Buffalo
Department
Type
Schools of Dentistry
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260
Dagenais, S L; Nakamura, I (1997) A physical map of the mouse H2 Bat5/Db interval. Mamm Genome 8:39-41
Zheng, W P; Kiura, K; Milisauskas, V K et al. (1996) Murine NK cell allospecificity-1 is defined by inhibitory ligands. J Immunol 156:4651-5
Zheng, W; Nakamura, I (1995) Immunological screening of homologous recombination in genes that encode surface antigens. Biotechniques 18:740-2
Zheng, W P; Kiura, K; Nakamura, I (1995) Dd is the only gene that controls NK cell resistance of heterozygous H-2b/d cells. Mol Immunol 32:773-6
Milisauskas, V K; Nakamura, I (1994) The ability of H-2Dd molecule to affect natural resistance to hemopoietic allografts is an intrinsic property shared by Ddm1 but not Ld. Eur J Immunol 24:336-42