WDFY4 is required for cross-presentation in response to viral and tumor antigens

Adding to the cross-presentation family Immune responses to viral or tumor antigens are typically initiated by the process of cross-presentation. Cross-presentation is believed to be the major way that innate immune cells, such as the classical dendritic cell 1 (cDC1) subset, activate and prime immunological T cells. Theisen et al. used CRISPR-based screening to identify regulators of cross-presentation by cDC1s (see the Perspective by Barbet and Blander). One such regulator that was identified, WDFY4 (WD repeat- and FYVE domain–containing protein 4), was required for cross-presentation of cell- and bacterial-associated antigens. WDFY4 played a critical role in cDC1-mediated viral and tumor immunity yet did not seem necessary for major histocompatibility complex class II presentation or for cross-presentation by monocyte-derived DCs. Science , this issue p. 694 ; see also p. 641