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

Pietro Crivello1, Nina Lauterbach, Laura Zito

  • 1Unit of Molecular and Functional Immunogenetics, San Raffaele Scientific Institute, Milan, Italy.

Human Immunology
|April 27, 2013
PubMed

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:
BLCLEpstein–Barr Virus transformed B lymphoblastoid cell linesGvHDHSCTLVMESFMFIMLRPBMCPCR-SSPPCR-sequence specific primingRST cell epitopeTCETMVUDgamma interferongraft versus host diseasehPGKhematopoietic stem cell transplantationhuman phosphoglycerate kinaselentiviral expression vectormedian fluorescence intensitymixed lymphocyte reactionmolecules of equivalent soluble fluorochromeperipheral blood mononuclear cellsresponder donorstimulator donortransmembranetruncated form of the human low affinity nerve growth factor receptorvolunteer unrelated donorsΔLNGFRγ-IFN

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