Delivery of lethal hits by cytotoxic T lymphocytes in multicellular conjugates occurs sequentially but at random times

Abstract

We propose a stochastic model to explain kinetic data on the delivery of lethal hits by cytotoxic T lymphocytes in multicellular conjugates. The comparison of our model with data of Zagury et al. suggests that cytotoxic T cells deliver lethal hits at random, and when conjugated to multiple target cels these cells attack undamaged target cells one at a time. The mean rate at which lethal hits are delivered per target cell is approximately the same for conjugates containing one or two target cells but slows substantially in conjugates containing three target cells. If our model is modified so that both previously hit and unhit target cells are susceptible to being lethally hit at the same rate, a very poor fit to Zagury et al's data is obtained. This leads us to conclude that previously hit cells are either not hit again or are hit at a substantially reduced rate.