LAUSR

Cross-presentation of exogenous particulate antigen is essential for the priming of CD8+ T cells and effective adaptive immunity to viruses and tumors. In Science, Theisen et al. identify a new player, the BEACH domain–containing protein WDFY4, that is expressed in CD8α +XCR1+ classical dendritic cells (cDC1s) and is necessary for their cross-presentation function. Although WDFY4-deficient mice develop cDC1s normally and can mount protective interleukin 12–dependent responses to Toxoplasma gondii, these mice fail to efficiently cross-present antigen for priming CD8+ T cells after viral or tumor challenge. WDFY4 localizes near the cytoplasmic face of the plasma membrane, co-localizing with clathrinand Rab11-containing vesicles. Protein co-immunoprecipitation assays suggest specific interaction between WDFY4 and the chaperone protein HSP90. The specific role of WDFY4 in cross-presentation remains to be delineated, but its identification provides a hook by which to investigate phagosomal antigen-processing pathways. LAD