In the immune system, stimulation and activation of lymphocytes depend on receptors that connect to intracellular signaling pathways via intermediary adapter proteins. Such receptors are classified according to whether they represent primary recognition structures or mediate secondary costimulatory signals. Two studies now suggest that NKG2D--a receptor used in both adaptive and innate immune responses--belongs to both classes.
Gilfillan et al. observed that, in mice lacking the known NKG2D adapter DAP10, functional NKG2D expression was lost on CD8+ T cells but was maintained on natural killer (NK) cells through use of a second adapter, DAP12. Diefenbach et al. provide an elegant mechanistic explanation for how this is achieved, by demonstrating that NKG2D is generated as two isoforms that associate differentially with DAP10 and DAP12; in addition, DAP12 expression was restricted to macrophages and NK cells. Through the use of alternative splicing of receptor and varied expression of adapters, these studies reveal how the one receptor functions either as a primary receptor in NK cells or as a costimulatory protein in T cells. -- SJS
Nature Immunol., 10.1038/ni857; 10.1038/ni858 (2002).
