A T-cell epitope encoded by a subset of HLA-DPB1 alleles determines nonpermissive mismatches for hematologic stem cell transplantation

Blood. 2004 Feb 15;103(4):1417-24. doi: 10.1182/blood-2003-04-1279. Epub 2003 Oct 23.


The importance of HLA-DPB1 matching for the outcome of allogeneic hematologic stem cell (HSC) transplantation is controversial. We have previously identified HLA-DPB1*0901 as a target of cytotoxic T cells mediating in vivo rejection of an HSC allograft. Here we show that HLA-DPB1*0901 encodes a T-cell epitope shared by a subset of DPB1 alleles that determines nonpermissive mismatches for HSC transplantation. Several T-cell clones obtained from the patient at the time of rejection showed HLA-DP restricted recognition of allogeneic targets expressing HLA-DPB1*0901, *1001, *1701, *0301, *1401, and *4501, but not other alleles. Based on these findings, we developed an algorithm for prediction of nonpermissive HLA-DPB1 mismatches. Retrospective evaluation of 118 transplantations showed that the presence of nonpermissive HLA-DPB1 mismatches was correlated with significantly increased hazards of acute grade II to IV graft-versus-host disease (HR = 1.87, P =.046) and transplantation-related mortality (HR = 2.69, P =.027) but not relapse (HR = 0.98, P =.939), as compared with the permissive group. There was also a marked but statistically not significant increase in the hazards of overall mortality (HR = 1.64, P =.1). These data suggest that biologic characterization of in vivo alloreactivity can be a tool for definition of clinically relevant nonpermissive HLA mismatches for unrelated HSC transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Alleles
  • Amino Acid Sequence
  • Cross Reactions
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology*
  • Graft vs Host Disease / immunology
  • HLA-DP Antigens / genetics
  • HLA-DP Antigens / immunology*
  • HLA-DP beta-Chains
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Isoantigens / genetics
  • Isoantigens / immunology
  • Molecular Sequence Data
  • Retrospective Studies
  • T-Lymphocytes / immunology


  • Epitopes, T-Lymphocyte
  • HLA-DP Antigens
  • HLA-DP beta-Chains
  • HLA-DPB1 antigen
  • Isoantigens