Inhibition of non MHC-restricted cytotoxicity of human NK cells and a CD8⁺αβ T cell clone by MHC class I cross-linking

The list of ligands that become receptors in the immune system is increasing every day. Our recent research has shown that aggregation of human MHC class I molecules by specific monoclonal antibodies on NK and cytotoxic T cells (CTL) inhibits non-specific lysis. These results suggest that human MHC class I molecules on effector NK/CTL cells could transmit inhibitory signals upon engagement with putative ligands expressed on the surface of those cells that need to be protected from non-specific cytotoxicity. Therefore human MHC I are not only ligands for antigen recognition or for other non-rearranged NK receptors, but are also signaling molecules either by themselves or through membrane colocalization with supramolecular activation clusters (SMACs) or through association with correceptors more directly involved in signal transduction. In addition our results could also have implications in the study of inhibitory signals modulating NK and T cell cytotoxicity where anti-MHC class I antibodies were extensively used. Overall, these results suggest a novel function of the multifarious human class I molecules that could have important implications in the study of regulatory signals that control effector NK and CTL cell activity.