MHC class I cross-talk with CD2 and CD28 induces specific intracellular signalling and leads to growth retardation and apoptosis via a p56(lck)-dependent mechanism

Ligation of the major histocompatibility complex class I molecules (MHC-I) on human T lymphoma cells (Jurkat) initiates p56(lck)-dependent intracellul ar signalling events (phosphotyrosine kinase activity; [Ca2+](i)) and leads to augmented growth inhibition and apoptosis. MHC-I ligation in concert wi th ligation of CD2 or CD28 augments, changes or modifies the pattern of act ivation. Ligation of MHC-I and CD2 alone resulted in growth inhibition, whe reas CD28 ligation alone had no effect on cell proliferation. Ligation of M HC-I together with CD2 augmented growth inhibition and enhanced the level o f apoptosis. In parallel experiments with the p56(lck)-negative Jurkat muta nt cell, JCaM1.6, cross-linking neither influenced cell signalling nor cell ular growth functions, indicating a cardinal role of the src kinases in sig nal transduction via MHC-I, CD2 and CD28 molecules. The results presented h ere provide evidence for the involvement of MHC-I molecules in the modulati on of signal transduction via the CD2 and CD28 costimulatory molecules. Cop yright (C) 1999 S. Karger AG, Basel.