Dissecting Genetic Control of HLA-DPB1 Expression and Its Relation to Structural Mismatch Models in Hematopoietic Stem Cell Transplantation.

摘要: HLA expression levels have been suggested to be genetically controlled by single nucleotide polymorphisms (SNP) in the untranslated regions (UTR), and variants associated with outcome of chronic viral infection hematopoietic stem cell transplantation (HSCT). In particular, 3'UTR rs9277534-G/A SNP HLA-DPB1 has graft-versus-host-disease after HSCT (Expression model); however its relevance different immune cells mode action not systematically addressed. addition, there is a strong though complete overlap between structural T epitope (TCE) groups which also (TCE Structural model). Here we confirm extend previous findings significantly higher B lines, unstimulated primary cells, monocytes homozygous for rs9277534-G compared those rs9277534-A. However, these differences were abrogated interferon-γ stimulation or differentiation into dendritic cells. We identify at least seven haplotypes differing total 37 SNP, characterized linkage length short tandem repeat (STR) intron 2 TCE group assignment. mapping did show any significant post-transcriptional regulation assessed luciferase assays two representative eight overlapping fragments. Moreover, no evidence alternative splicing STR was obtained RT-PCR. an exemplary cohort 379 mismatched donor-recipient pairs, risk prediction Expression model 36.7% concordant, majority discordances due non-applicability model. from expressed absence similar transfected HeLa elicited mean alloreactive CD4+ T-cell responses, as CD137 upregulation 178 independent cultures. Taken together, our data provide new insights type-specific mechanistic basis association expression, that, despite partial both models risk-prediction, differential alloreactivity determined occurs independently expression.