MR1 rs2236410 mediates the regulation of mucosal-associated invariant T cells against graft-versus-host disease

Abstract Major histocompatibility complex class 1-related gene protein (MR1) is a monomorphic antigen-presenting molecule. Mucosal associated invariant T (MAIT) cells are an unconventional T cells subset limited to the antigen-presenting molecule MR1. MR1 rs2236410 site of single nucleotide polymorphism (SNP) is reported that locates in the MR1 antigen binding region and is identified as HLA Class II restricted minor histocompatibility antigen, which is associated with transplantation immunity. Here, we found that the donor rs2236410A/G genotype was associated with a lower incidence of severe or gut acute graft-versus-host disease (GVHD) in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) clinical cohort. Through in vitro E. coli stimulation experiments, it was found that MR1 rs2236410 mediated the activation of MR1-dependent pathway of MAIT cells by influencing the presentation of microbial derived ligand, thus affecting the anti-GVHD effect of MAIT cells. These findings suggest that MR1 rs2236410 could serve as a potential immune target for antiGVHD without affecting the GVL effect in the context of transplantation, which could provide certain guidance for the prediction and clinical treatment of GVHD.