Long-Term Objective: It is the long-term objective of this proposal to clarify biologic functions of the products of the B2m region, particularly their collaborative functions with the products of the MHC. The information that is generated on the B2m region and its relationship to the H-2 complex will contribute to a better understanding of the role of gene duplication, chromosomal translocation and chromosomal duplication in the evolution of the mammalian genome.
Specific Aim : It is the specific aim of this proposal to elucidate the genetic fine structure of the B2m region. In order to achieve this end B2m region recombinant mice will be produced as well as cytotoxic T lymphocyte (CTL) lines and clones and monoclonal antibodies specific for B2m region antigens. These mouse strains and reagents will be of value to all scientists working in this area. Methodology: Appropriate mouse strains will be produced using the breeding techniques developed by Snell. We will use standard allograft rejection CML, MCL, IL-2, dye exclusion cytotoxicity and Elisa assays. We will use those techniques described in the literature to produce lymphocyte clones and hybridomas, to solubilize membrane antigen and to produce cDNA clones and to study genomic DNA. For those areas where we have been unsuccessful (Production of antibody) or where we are inexperienced (solubilization of membrane antigen and molecular genetic techniques) we will obtain expert consultation. Health Relatedness: Manipulation of the immune system is used in modern health care in ways too numerous to be recounted. Scientists are attempting to expand the use of such manipulations into new areas in the simplest terms to develop methods of inducing individuals to mount effective responses against pathogens such as the AIDS virus and against the tumor specific antigens of neoplasms. An improved understanding of the mechanisms of the immune system will aid in such development.
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| 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 |
