Our long term goal is to understand how genes in the major histocompatibility complex regulate immun responses to viruses tumor cells and allogeneic cells. Toward this end we have chosen to embark on a detailed structure/function study of a mouse major histocompatibility class I gene. We will focus on the application of saturation mutagenesis techniques and the functional analysis of the mutants produced using specific anitibodies and T cells. The ability to produce and analyze large numbers of these mutants has been made possible by the application of techniques from modern nucleic acid chemistry coupled to molecular biology. We have already produced a library of mutant class I genes containing all possible single base substitutions in exon 2 of the DP gene. Additional analyses of this library and the production of other mutant libraries are proposed. We will also extend our studies on a non-classical class I gene, Q4. We will determine patterns of expression of Q4 molecules. Q4 specific RNA level is widely expressed in the tissues of adult mice. Experiments are proposed to investigate the cell biology of Q4 as well as its regulation during development and response to exogenous stimulatory factors. We believe these experiments will contribute to a better understanding of the role of the MHC in immunobiology and transplantation.
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