HLA-mismatched patient-unrelated donors may encode variation in regions between classical HLA loci. HLA-matched patients and donors may encode different sequences in between the HLA-A, C, B, DRB1, and DQB1 loci, and these variants may be a source of disparity that gives rise to GVHD after HCT.⁴⁰  In HLA-mismatched HCT, the frequency of patient-donor sequence differences and the extent of the MHC that is different may be pronounced, and the effects of such untyped variation may be additive to that from the patient-donor HLA mismatch.⁴¹