The aim of this application is to support research in four projects focused on the recognition of antigen by antigen specific, major histo-compatibility complex (MHC)-restricted T cells and the biochemical events in T cells subsequent to such recognition. Funds are also requested for the support of two core facilities and the purchase of major equipment essential to the projects outlined in this application and to other related research funded in the laboratories of the investigators named on this application and others.
The aim of the first research project is to produce a collection of monoclonal antibodies specific for allelic, isotypic or common determinants on antigen-specific, MHC-restricted receptors on mouse T cells. These antibodies will then be used by us, and made available to other laboratories, for genetic, ontogenetic, biochemical and functional studies on T cell receptors. Experiments planned in the second research project will study the antigenic and structural relationships between T cell receptors and products of the MHC. The third project contains four series of experiments designed to study requirements for antigen presentation to T cells. Included in these studies will be the role of """"""""accessory"""""""" molecules, the effects of lipid content in the antigen presenting membrane, the nature of Mls antigens and the targets of concanavalin A. The fourth research project involves the study of biochemical events in T cells after they have been activated via their receptors. The first of the two core facilities described in this application includes a cytofluorograf essential to the work described here, and many of our other experiments. In year two monies are requested for the purchase of a dye laser which will greatly increase the usefulness of the instrument. Funds are also requested for a """"""""chemical core"""""""" comprised of a protein sequencer, and oligonucleotide and peptide synthesizer. The first of these instruments is already operational and in full use. Money is requested for the purchase of the last two instruments in the first year of this project. This program will contribute invaluably to our ability to study early events in T cell activation, a phenomenon which is fundamental to understanding how the immune response is initiated and controlled.
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