Effects of transmembrane region variability on cell surface expression and allorecognition of HLA-DP3.
Hum Immunol
; 74(8): 970-7, 2013 Aug.
Article
em En
| MEDLINE
| ID: mdl-23619468
ABSTRACT
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(*)0301 and DPB1(*)10401. 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 4.21. 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(*)0301 and DPB1(*)10401, 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.
Palavras-chave
BLCL; EpsteinBarr 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
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cadeias beta de HLA-DP
Limite:
Humans
Idioma:
En
Revista:
Hum Immunol
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Itália