The ultimate goal of this research is to define the human cytolytic T lymphocyte (CTL) response to leukemia by utilizing purified and well-characterized antigens, cloned CTL lines, and monoclonal antibodies to functional T-cell subsets. In order to better understand the CTL response, it is necessary to define the antigens that trigger this response and to define the cell interactiona that regulate this response. Since CTLs appear in all cases studied to respond to integral membrane proteins (whether they be foreign MHC antigens or autologous MHC antigens in association with foreign antigens such as a virus), it has been difficult to define the antigens involved in CTL triggering. Initial studies in murine xenogeneic, allogeneic, and syngeneic CTL model systems demonstrate that H-2 and HLA antigens can be isolated from the cell surface and retain CTL stimulating activity. These results suggest that the antigenic requirements for the stimulation of human CTLs can be approached in a similar manner. The ability to obtain cloned CTL lines should allow one to define more precisely the specificity of CTLs. Thus, one can hope to determine what target antigens are recognized by monoclonal CTLs when triggered by well-defined antigens, i.e., purified MHC antigens or purified viral antigens plus MHC antigens inserted into artificial membranes or liposomes. The ability to obtain cloned helper T cells or suppressor T cells should also allow a more careful delineation of the cell-cell interactions that regulate the CTL response. These cloned functional T-cell lines may provide the appropriate reagents to raise antibodies to antigens specific for functional subsets of T cells. The availability of antibodies to human CTLs should subdivide the T-cell subset defined by OKT5 and OKT8 and allow a separation of CTLs from suppressor T cells. These new reagents may also allow us to isolate biochemically and define these cell surface antigens, possibly even resulting in the isolation and characterization of functional T-cell receptors. (LB)

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Experimental Immunology Study Section (EI)
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Dana-Farber Cancer Institute
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