The aim of this program project is to support research in 6 projects focussed on the recognition of antigen by T cells. Funds are also requested for the support of a flow cytometric and a chemistry core facility. The former facility provides for analysis and sorting of cells, and includes 2 cell sorters, the latter facility includes a peptide and an oligonucleotide synthesiser and a protein sequencer. The first project will continue to produce monoclonal antibodies against the T cell receptor/T3 complex. These will be used to investigate the elements controlling the T cell repertoire in different mouse strains and in studies on the structure and function of the T cell receptor/T3 complex (Projects 1, 4 and 5. The second project will continue to investigate one of the phenomena which does control the T cell repertoire, namely the interaction between MHC products, T cell receptors which bind them, and T cell receptors which mimic them. Studies will focus on the control of T cell repertoire by other T cells. Also included are experiments to test the diversity of receptors on and functions of gamma delta-bearing cells. The third project deals with the presentation of peptides from globular, soluble proteins in association with class I MHC products to cytotoxic T cells. The goal is to compare this process to the presumably related and better understood mechanisms of Class II presentation of the same or similar peptides. Project 4 concerns events that happen inside the T cell after activation. A cell free system will be used to find out which components of the T cell receptor complex are involved in transducing signals to the interior of the T cell, consequent on the binding of antigen/MHC to the T cell receptor. Studies in the fifth project address the structure of the T cell receptor/T3/antigen/MHC and possibly CD4 complex. Crosslinking reagents and antibodies will be used to find out which components are bound to which in complexes prepared from isolated proteins and intact cells. Dr. Palmer and his collaboration have shown that a particular V alpha family, V alpha7, is used with very low frequency by peripheral T cells. Experiments in the sixth project will test whether this is due to some defect in the genes encoding this family, or to post-gene rearrangement control of T cells bearing V alpha7 via restriction and/or tolerance.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program Projects (P01)
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