Host dendritic cells are thought to be critical for the initial activation of alloreactive donor T cells and initiation of GVHD after allogeneic hematopoietic transplantation. Toubai et al use a series of experimental models, including transplantation with H-Y antigen-specific Mata Hari T cells, to demonstrate that host hematopoietic antigen-presenting cells may not be essential for initiation of GVHD. Professional illustration by Kenneth X. Probst.