The long term objective of this research proposal is to understand at the molecular and cellular levels how the immune recognition is controlled during the organism's development.
Specific aims are: 1) to understand the molecular mechanism of the tissue-specific enhancer associated with the immunoglobulin gene locus, 2) to identify the cis- and trans-acting elements involved in the developmentally controlled expression of the T cell receptor Alpha and Beta genes and the T cell-specific gene Gamma, 3) to identify, isolate, and characterize the genes and gene products for the putative receptor on the immature T cells involved in the intrathymic selection of self MHC-restricted T cells. For these purposes we will use a variety of recombinant DNA, DNA sequencing, transfection, cell-free transcription, hybridoma, and transgenic mice techniques as well as more conventional biochemical techniques for proteins and nucleic acids. Since the B and T cell receptors play the pivotal roles in the functioning of the immune system, the vertebrate's major body defense device, through understanding of the developmentally controlled expression of the genes is the basis on which a variety of diagnostic and therapeutic methods can be developed. In addition, the information on the structure and function of anti MHC receptor will be useful in the clinical control of the allograft rejection.
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