Effects of transmembrane region variability on cell surface expression and allorecognition of HLA-DP3

Hum Immunol. 2013 Aug;74(8):970-7. doi: 10.1016/j.humimm.2013.04.014. Epub 2013 Apr 23.


The functional relevance of polymorphisms outside the peptide binding groove of HLA molecules is poorly understood. Here we have addressed this issue by studying HLA-DP3, a common antigen relevant for functional matching algorithms of unrelated hematopoietic stem cell transplantation (HSCT) encoded by two transmembrane (TM) region variants, DPB1(*)03:01 and DPB1(*)104:01. The two HLA-DP3 variants were found at a overall allelic frequency of 10.4% in 201 volunteer stem cell donors, at a ratio of 4.2:1. No significant differences were observed in cell surface expression levels of the two variants on B lymphoblastoid cell lines (BLCL), primary B cells or monocytes. Three different alloreactive T cell lines or clones showed similar levels of activation marker CD107a and/or CD137 upregulation in response to HLA-DP3 encoded by DPB1(*)03:01 and DPB1(*)104:01, either endogenously on BLCL or after lentiveral-vector mediated transfer into the same cellular background. These data provide, for the first time, direct evidence for a limited functional role of a TM region polymorphism on expression and allorecognition of HLA-DP3 and are compatible with the notion that the two variants can be considered as a single functional entity for unrelated stem cell donor selection.

Keywords: BLCL; Epstein–Barr Virus transformed B lymphoblastoid cell lines; GvHD; HSCT; LV; MESF; MFI; MLR; PBMC; PCR-SSP; PCR-sequence specific priming; R; S; T cell epitope; TCE; TM; VUD; gamma interferon; graft versus host disease; hPGK; hematopoietic stem cell transplantation; human phosphoglycerate kinase; lentiviral expression vector; median fluorescence intensity; mixed lymphocyte reaction; molecules of equivalent soluble fluorochrome; peripheral blood mononuclear cells; responder donor; stimulator donor; transmembrane; truncated form of the human low affinity nerve growth factor receptor; volunteer unrelated donors; ΔLNGFR; γ-IFN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Gene Expression
  • Gene Frequency
  • Genetic Variation
  • HLA-DP beta-Chains / genetics*
  • HLA-DP beta-Chains / metabolism*
  • Histocompatibility / genetics
  • Histocompatibility / immunology
  • Histocompatibility Testing
  • Humans
  • Immunophenotyping
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Unrelated Donors


  • HLA-DP beta-Chains
  • HLA-DPw3 antigen