DAP12-deficient mice fail to develop autoimmunity due to impaired antigen priming

DAP12 is an ITAM-bearing membrane adaptor molecule implicated in the activa tion of NK and myeloid cells. In mice rendered DAP12 deficient by targeted gene disruption, lymphoid and myeloid development was apparently normal, al though the activating Ly49 receptors on NK cells were downregulated and non functional. To analyze the consequences of DAP12 deficiency in vivo, we exa mined the susceptibility of DAP12(-/-) mice to experimental autoimmune ence phalomyelitis (EAE). DAP12-/- mice were resistant to EAE induced by immuniz ation with myelin oligodendrocyte glycoprotein (MOG) peptide. Resistance wa s associated with a strongly diminished production of IFN gamma by myelin-r eactive CD4(+) T cells due to inadequate T cell priming in vivo. These data suggest that DAP12 signaling may be required for optimal antigen-presentin g cell (APC) function or inflammation.