MHC-I-induced apoptosis in human B-lymphoma cells is dependent on protein tyrosine and serine/threonine kinases

In addition to providing the framework for peptide presentation, major hist ocompatibility complex class I (MHC-I) molecules can act as signal transduc ing molecules in lymphoid cells. Here we show that the mobilization of intr acellular calcium, which follows: crosslinking of MHC-I molecules on human B lymphoma cells, is dependent on protein tyrosine kinases and the phosphat idylinositol 3 (PI-3) kinase. Functional studies showed that MHC-I crosslin king induced almost complete inhibition of the spontaneous proliferation of the B lymphoma cells as early as 6 h post-crosslinking and apoptosis 24 h post-crosslinking. Preincubation with either protein tyrosine kinase or pro tein serine/threonine kinase inhibitors reduced the MHC-I-induced apoptosis to background levels, whereas inhibition of PI-3 kinase had no effect. The se data demonstrate a pivotal role for protein tyrosine and serine/threonin e kinases in MHC-I-mediated apoptosis in human B-cells and suggest the pres ence of several MHC-I signaling pathways leading to diverse effects in thes e cells. (C) 1999 Academic Press.