TY - JOUR
T1 - Effects of transmembrane region variability on cell surface expression and allorecognition of HLA-DP3
AU - Crivello, Pietro
AU - Lauterbach, Nina
AU - Zito, Laura
AU - Sizzano, Federico
AU - Toffalori, Cristina
AU - Marcon, Jessica
AU - Curci, Laura
AU - Mulder, Arend
AU - Wieten, Lotte
AU - Zino, Elisabetta
AU - Voorter, Christien E. M.
AU - Tilanus, Marcel G. J.
AU - Fleischhauer, Katharina
PY - 2013/8
Y1 - 2013/8
N2 - 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*1 04:01. 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.
AB - 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*1 04:01. 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.
U2 - 10.1016/j.humimm.2013.04.014
DO - 10.1016/j.humimm.2013.04.014
M3 - Article
C2 - 23619468
SN - 0198-8859
VL - 74
SP - 970
EP - 977
JO - Human Immunology
JF - Human Immunology
IS - 8
ER -