The double life of NK receptors: stimulation or co-stimulation?

Stimulatory killer immunoglobulin-like receptors, NKG2D and stimulatory receptors of the CD94-NKG2 family have duplicity in function. On natural killer (NK) cells, these receptors act as independent and competent recognition units. Stimulatory NK receptors also appear on subsets of effector T cells, particularly those that have replicated extensively. When expressed on T cells, they amplify signals mediated through the T-cell antigen receptor and, thus, function as co-stimulatory, but not direct stimulatory, molecules. One mechanism responsible for this dichotomy is the differential expression of adaptor molecules. This duplicity in function, which is not seen for other co-stimulatory molecules, is responsible for the unique context information provided by the NK receptors, and it could explain their involvement in chronic inflammation and autoimmunity.