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.
Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.