MOLECULAR GENETIC ANALYSIS OF LYMPHOCYTE FUNCTION

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The ongoing focus of the laboratory is to understand in detail the structure/function relationships of cell surface molecules involved in the immune response. In particular, we have made significant progress over the past year in several areas: A. generating a panel o molecularly engineered soluble counterparts of the murine class I major histocompatibility antigens H-2Kb, H-2Dd, H-2Ld, H- 2Kk, H-2Kbm6, H-2Kbm8, H-2Kbm10, and the human class I MHC molecule HLA-A2; B. using these soluble molecules to study he biochemical requirements for activation of allospecific T lymphocytes; C. using these soluble molecules to estimate the affinity of an H-2Kb- reactive T cell receptor for the H-2Kb molecule; D. identifying a region of the class I molecule that appears to be a major T cell receptor binding site; E. studying he binding of antigenic viral peptides to purified soluble MHC class I molecules; F. producing transgenic mice that express a soluble counterpart of the soluble H-2Dd molecule to study fundamental questions of the generation of T cell tolerance and education; G. developing a strategy for the production of soluble counterparts of membrane molecules allowing dimeric production and simple purification.