Human Cytolytic T-Lymphocyte Clones and Their Function-Associated Cell Surface Molecules

Abstract

Cytolytic T lymphocytes (CTLs) are important effectors in the recognition of viruses,1 allografts,2 and some tumors.3 A molecular understanding of the CTL-target cell interaction therefore may be relevant to the etiology and/or treatment of a variety of disease states. Tissue culture techniques, first reported by Gillis and Smith,4 have allowed the generation of long-term T-cell lines that retain function. A number of human long-term cytolytic T lymphocyte lines have been generated by continued stimulation of peripheral blood lymphocyte lines with “foreign” cells in the presence of the T-cell growth factor interleukin 2 (IL-2).5,6 We have used CTL lines and clones to define target antigens recognized by human allogeneic lymphocytes, to correlate lymphocyte phenotype with antigen specificity, and to generate monoclonal antibodies that block lymphocyte function. Our findings have provided new insights into the cell surface molecules involved in the CTL-target cell interaction. In this chapter we describe our methodologies for the generation and maintenance of CTL lines and clones and the use of the cells in concert with monoclonal antibodies to define and analyze function-associated cell surface molecules.