Degradation of specificity in cytolytic T lymphocyte clones: two broad specificity, H-2-independent recognition systems, one natural killer-like, develop during culture, in addition to the clonally distributed antigen-specific receptor

Abstract

Ly-2+ CBA mouse T lymphocytes stimulated with concanavalin A in limiting dilution culture produce clones of cytotoxic T lymphocytes (CTL) which, although initially specific, eventually lyse a wide range of target cells. The nature of the recognition system for this apparently "nonspecific" cytolysis was examined using a range of tumor cells as labeled targets and as cold target inhibitors. Most syngeneic and allogeneic murine tumor cells were lysed but the degree of lysis varied, even for different sublines of the same tumor. All tumor cells cold target inhibited their own lysis, and cross-inhibited lysis of other targets to varying degrees. The recognition stage of "nonspecific" cytolysis appeared to be independent of target cell H-2 expression; some H-2-negative murine target cells were lysed and some were not, but all gave cold target inhibition of "nonspecific" cytolysis. Xenogeneic tumor cells were resistant to lysis, but some nevertheless gave cold target inhibition of the "nonspecific" cytolysis of murine targets. A study of the specificity of cold target cross-inhibition revealed two distinct patterns of recognition which existed simultaneously in "nonspecific" CTL; one was like that of natural killer cells and was directed to targets such as YAC-1, the other was distinct from that of natural killer cells and was directed to targets such as P815. Thus, murine CTL may express three distinct receptors, the clonally distributed, H-2-restricted, antigen-specific T cell receptor and two different "broad-range" receptors common to most clones.