Despite the low expression level of HLA-C, HLA-C mismatches are clearly associated to alloreactivity after hematopoietic stem-cell transplantation (HSCT): in a number of large cohorts HLA-C mismatches are correlated to an increased risk of acute graft-versus-host disease (GVHD) or even impaired survival (Figures 1A,B) (9–13). Here, HLA-C is linked to acute graft versus host disease.