When the donor and recipient are mismatched at HLA-DPB1, the risk of graft-versus-host disease is high. The authors found that when the donor has a particular regulatory allele that lowers expression of HLA-DPB1, the risk of GVHD is lower. Hematopoietic-cell transplantation from unrelated donors can cure blood disorders; however, graft-versus-host disease (GVHD) remains a major impediment to successful outcomes. 1 GVHD can occur after HLA-matched transplantation when the donor cells recognize polymorphic peptides (“minor histocompatibility antigens”) presented by the recipient’s HLA. 2 In HLA-mismatched transplantation, direct recognition of the recipient’s mismatched HLA by the donor’s cells provides a potent stimulus for graft-versus-host allorecognition 3 – 7 ; recognition of the donor’s mismatched HLA by the recipient’s immune system leads to graft rejection. 8 , 9 The importance of HLA class II alloantigens was established early in the history of clinical transplantation. 10 Advances in understanding the . . .