Natural killer cell licensing during viral infection.

Natural Killer (NK) cell functionality is controlled by inhibitory receptors that recognize self-MHC class I. NK cells that do not interact with self-MHC class I are hypo-responsive to many stimuli and fail to reject MHC class I-deficient cells. Thus, although the mechanisms are unknown, interactions with MHC class I "licensed" NK cells respond efficiently. Surprisingly, these licensed NK cells fail to control viral infection. During mouse cytomegalovirus (MCMV) infection, SHP-1 signaling downstream of inhibitory receptors for MHC class I limits NK cell proliferation. Interactions with MHC class I prevent licensed NK cells from controlling of MCMV replication and pathogenesis; rather, it is the unlicensed NK cells that are not inhibited by self-MHC class I that efficiently control MCMV infection. Therefore, the licensing hypothesis is not sufficient to explain NK cell functionality during viral infection.