The continuum from experimental observation, to the development of a concept, to the clinical reflection of that concept has been particularly prominent in transplantation biology. Cell membrane antigens which had been studied for prolonged periods without knowledge of their purposes are now being assigned functions and associations. Of the 42 identified murine histocompatibility genes, 17 have been located in four clusters. The MHC cluster, the most studied of the four, includes the H-2 complex and the linked H-33 and H-39 loci. Products of the genes of the MHC cluster are involved in the complement cascade as well as the immunological system. The chromosome 2 cluster also has been shown to be involved in both systems. However, the data are sparse and confusing. It is our specific objective to generate more data concerning the genetic control, immunogenicities and function of the products of the chromosome 2 cluster. In so doing, this proposal will contribute to a better understanding of the genetic significance of such features of the mammalian chromosome as genes with related functions within clusters as well as clusters with related functions on different chromosomes, and the evolutionary role of chromosomal duplications and translocations in generating such clusters.
Our specific aims are as follows: 1. Characterization of existing chromosome 2 congenics will be completed. 2. Chromosome recombinant congenic mouse strains will be produced and characterized. 3. The relationship between the antigens of chromosome 2 will be investigated using allograft rejection, CML (by conventional and cloned CTL's), and serologic (by conventional and monoclonal antibodies) techniques. 4. The immune response to the antigens of chromosome 2 will be studied. 5. The immune response genes of chromosome 2 will be studied.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI021000-02
Application #
3130882
Study Section
Immunobiology Study Section (IMB)
Project Start
1984-09-01
Project End
1987-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Barnes-Jewish Hospital
Department
Type
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63110
Graff, R J; Hauptfeld, V; Riordan, K et al. (1994) Continued mapping of chromosome 2 genes. Immunogenetics 40:21-6
Graff, R J; Kurtz, M E; Paul, R et al. (1991) Additional mapping of mouse chromosome 2 genes. Immunogenetics 33:96-100
Graff, R J; Kurtz, M E; Russell, H et al. (1988) Time-response studies of the cellular immune response to cell membrane antigens. Transplantation 45:479-84
Graff, R J; Martin-Morgan, D; Kurtz, M E (1987) Multiplicity of chromosome 2 histocompatibility genes: new loci, H-44 and H-45. Immunogenetics 26:111-4
Kurtz, M E; Martin-Morgan, D; Graff, R J (1987) Recognition of the beta-2 microglobulin-B molecule by a CTL clone. J Immunol 138:87-90
Graff, R J; Simmons, D; Meyer, J et al. (1986) Abnormal bone production associated with mutant mouse genes pa and we. J Hered 77:109-13