MOLECULAR GENETIC ANALYSIS OF LYMPHOCYTE FUNCTION

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The focus of these studies has been on the functional role of the MHC class I molecule and its interactions with T cell receptors. Model systems have been developed for studies of these functions in vivo and in vitro. Accomplishments during the past year include: 1) quantitative measurement of the interactions between purified T cell receptors and purified MHC class I molecules complexed with a panel of antigenic peptides; 2) engineering of large amounts highly purified T cell receptor domains, and their use for crystallization and functional studies; 3) evaluation of the interaction of soluble H-2Dd with NK cells bearing the Ly-49 surface protein. These studies are providing a new quantitative understanding of the binding interactions between MHC class I-peptide complexes and the receptors of T lymphocytes and NK cells. They may also help produce a detailed structure of the T cell receptor. Together, these investigations will help develop a more complete molecular picture of how immune recognition events involving MHC class I molecules contribute to regulation of the functions of these two important effector cell types.