Allorecognition of HLA-DP by CD4+ T cells is affected by polymorphism in its alpha chain

Mol Immunol. 2014 May;59(1):19-29. doi: 10.1016/j.molimm.2013.12.006. Epub 2014 Jan 22.


Alloreactivity to HLA-DP molecules, class II heterodimers of an oligomorphic alpha and a polymorphic beta chain, is increasingly being studied due to its relevance in clinical transplantation. We hypothesized that not only polymorphisms in the peptide binding groove encoded by exon 2 of HLA-DPB1, but also in other regions of the molecule and the alpha chain, could play a role in CD4+ T cell allorecognition. To test this possibility, we comparatively investigated CD4+ T cell allorecognition, measured by upregulation of the activation marker CD137, against HLA-DPB1*13:01, *05:01, *03:01, *17:01 or their allele counter parts DPB1*107:01, *135:01, *104:01, *131:01, with identical exon 2 sequences but polymorphism in exons 1, 3 or 4, in the context of different HLA-DPA1 (DPA1) polymorphisms (DPA1*01:03 and *02:01). No significant differences in CD4+ T cell allorecognition levels could be demonstrated for any of the beyond exon 2 DPB1 variants studied. Interestingly, however, the mean fold change in CD4+ CD137+ cells was significantly higher when the target shared at least one DPA1 allele with the allogeneic stimulator, compared to a distinct DPA1 background (1.65 vs 0.23, P<0.005). Structural homology modeling suggested specific amino acid residues in the alpha chain, in particular position 31, to impact CD4+ T cell allorecognition of HLA-DP. Our data argue against a significant role of beyond exon 2 DPB1 polymorphisms for T cell alloreactivity, but show relevance of DPA1 polymorphism in this mechanism. These new findings impact HLA matching strategies in unrelated stem cell transplantation.

Keywords: Allorecognition; HLA-DPA1; HLA-DPB1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Cell Line
  • Exons / genetics
  • HLA-DP Antigens / classification
  • HLA-DP Antigens / genetics
  • HLA-DP Antigens / immunology*
  • HLA-DP alpha-Chains / classification
  • HLA-DP alpha-Chains / genetics
  • HLA-DP alpha-Chains / immunology*
  • HLA-DP beta-Chains / classification
  • HLA-DP beta-Chains / genetics
  • HLA-DP beta-Chains / immunology
  • Histocompatibility / genetics
  • Histocompatibility / immunology
  • Histocompatibility Testing / methods
  • Humans
  • Polymerase Chain Reaction
  • Polymorphism, Genetic / immunology*
  • Sequence Analysis, DNA
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism


  • HLA-DP Antigens
  • HLA-DP alpha-Chains
  • HLA-DP beta-Chains
  • HLA-DPA1 antigen
  • HLA-DPB1 antigen