Kinetic Analysis of Target Cell Destruction by Effector T Cells

Abstract

Abstract Attempts have been made to test the hypothesis that the affinity of the effector T cell's antigen receptor changes in a predictable manner with respect to the dose of antigen used to elicit effector cells and with time after antigen exposure. Although we made no direct measurement of the affinity of the antigen receptor we have measured changes in the Kh parameter of cytolytically active lymphocyte populations. We demonstrate that this term, analogous to the Km value of enzymes, is an avidity parameter, reflecting the interaction rate of killer cells with homologous targets. We presume therefore that Kh values of killer T cells reflect the affinity of the cell's antigen receptor site. Low doses of alloantigen elicited few killer cells of high avidity (low Kh). Killer cell avidity varied inversely with effector cell frequency, reaching minimum avidity when killer cells were present in greatest numbers. There was, however, no constant propertionality between avidity and frequency. We suggest that these findings imply that T cell antigen receptors are heterogeneous with respect to their affinity for antigen and that clones of cells with receptors of high affinity are selected out when antigen is limiting. This selection is entirely analogous to that previously reported to operate for B cell clones and their product, serum antibody.