Ligation of major histocompatibility complex class I antigens (MHC-I) prevents apoptosis induced by Fas or SAPK/JNK activation in T-lymphoma cells.

Abstract

Early apoptosis in Jurkat T-lymphoma cells was induced by agonistic anti-Fas Ab or by anisomycin which activates the stress kinases SAPK/JNK. Apoptosis was inhibited by ligation of major histocompatibility complex class I antigens (MHC-I). MHC-I ligation induced upregulation of the anti-apoptotic Bcl-2 protein and stabilized the mitochondrial membrane potential (Deltapsim). MHC-I ligation also prevented downregulation of Bcl-2 and destabilization of Deltapsim induced by anti-Fas Ab treatment or anisomycin exposure. Studies on three different Jurkat cell mutants deficient for src p56(lck), ZAP-70 kinase, or TCR/CD3 gamma-chain showed that the cells undergo apoptosis after Fas ligation. Anisomycin exposure induced apoptosis in the src p56(lck)-deficient cell line but not in the two other mutant cell lines. Simultaneous cross-linking of MHC-I and Fas ligation inhibited apoptosis in the ZAP-70 kinase and the TCR/CD3 gamma-chain mutants, but did not protect the src p56(lck)-deficient cells. Similarly, MHC-I ligation did not protect anisomycin-treated src p56(lck)-deficient cells against apoptosis. These data suggest that MHC-I-induced inhibition of apoptosis depends on intact src p56(lck) activity, but not on major secondary messenger molecules associated with TCR signaling. Overall the results support the idea that signal transduction by MHC-I molecules is involved in homeostatic processes of importance for T-cell survival and death.