Physiological roles of murine DAP10 adapter protein in tumor immunity and autoimmunity.

The immune system has evolved to tolerate what is self and reject what is foreign. The recognition of self from non-self is performed by activating and inhibitory receptors, which signal immune cells via adapter molecules, determining the outcome of the immune response. DAP10, a transmembrane adapter protein expressed broadly in hematopoietic cells, associates with NKG2D activating receptor forming a multisubunit complex, which recognizes self-proteins upregulated during tumorigenesis, infection, and autoimmune response. Analysis of immune reactions against syngeneic tumors, as well as autoimmune responses in the DAP10-deficient mice, revealed an important physiological role of DAP10 signaling in maintaining tolerance to self, probably by controlling the development and activation threshold of autoreactive T cells.