PMID- 29025906 OWN - NLM STAT- MEDLINE DCOM- 20190724 LR - 20190724 IS - 1592-8721 (Electronic) IS - 0390-6078 (Print) IS - 0390-6078 (Linking) VI - 103 IP - 1 DP - 2018 Jan TI - Comparative profiling of HLA-DR and HLA-DQ associated factor VIII peptides presented by monocyte-derived dendritic cells. PG - 172-178 LID - 10.3324/haematol.2017.175083 [doi] AB - The development of anti-factor VIII antibodies is a major complication of the treatment of patients with hemophilia A. Generation of high affinity anti-factor VIII antibodies is dependent on help provided by CD4(+) T cells that recognize factor VIII-derived peptides presented on class II major histocompatibility complex on the surface of antigen-presenting cells. In order to identify the immune-dominant epitopes that can be presented to CD4(+) T cells, we previously developed a mass spectrometry-based method to identify factor VIII-derived peptides that are presented on human leukocyte antigen (HLA)-DR. In the present work, we compared the repertoire of FVIII-derived peptide presented on HLA-DR and HLA-DQ. Monocyte-derived dendritic cells from nine HLA-typed healthy donors were pulsed with recombinant factor VIII. HLA-DR and HLA-DQ molecules were purified using monoclonal antibodies. Our data show that HLA-DQ and HLA-DR present a similar repertoire of factor VIII-derived peptides. However, the number of peptides associated with HLA-DQ was lower than that with HLA-DR. We also identified a peptide, within the acidic a3 domains of factor VIII, which is presented with higher frequency on HLA-DQ. Interestingly, this peptide was found to have a higher predicted affinity for HLA-DQ than for HLA-DR. Taken together, our data suggest that HLA-DQ participates in the presentation of factor VIII peptides, thereby contributing to the development of inhibitory antibodies in a proportion of patients with severe hemophilia A. CI - Copyright(c) 2018 Ferrata Storti Foundation. FAU - Peyron, Ivan AU - Peyron I AD - Department of Plasma Proteins, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, the Netherlands. FAU - Hartholt, Robin B AU - Hartholt RB AD - Department of Plasma Proteins, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, the Netherlands. FAU - Pedro-Cos, Laura AU - Pedro-Cos L AD - Department of Plasma Proteins, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, the Netherlands. FAU - van Alphen, Floris AU - van Alphen F AD - Department of Research Facilities, Sanquin Research Amsterdam, the Netherlands. FAU - Brinke, Anja Ten AU - Brinke AT AD - Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, the Netherlands. FAU - Lardy, Neubury AU - Lardy N AD - Department of Immunogenetics, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, Amsterdam, the Netherlands. FAU - Meijer, Alexander B AU - Meijer AB AD - Department of Plasma Proteins, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, the Netherlands. AD - Department of Research Facilities, Sanquin Research Amsterdam, the Netherlands. AD - Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, the Netherlands. FAU - Voorberg, Jan AU - Voorberg J AD - Department of Plasma Proteins, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, the Netherlands j.voorberg@sanquin.nl. AD - Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, the Netherlands. LA - eng PT - Journal Article DEP - 20171012 PL - Italy TA - Haematologica JT - Haematologica JID - 0417435 RN - 0 (HLA-DQ Antigens) RN - 0 (HLA-DR Antigens) RN - 0 (Peptides) RN - 0 (Proteome) RN - 839MOZ74GK (F8 protein, human) RN - 9001-27-8 (Factor VIII) MH - Antigen Presentation/*immunology MH - Antigen-Presenting Cells/immunology/metabolism MH - Dendritic Cells/*immunology/*metabolism MH - Factor VIII/chemistry/*immunology MH - Gene Expression Profiling MH - HLA-DQ Antigens/genetics/*immunology MH - HLA-DR Antigens/genetics/*immunology MH - Hemophilia A/genetics/immunology MH - Humans MH - Peptides/*immunology MH - Proteome MH - Proteomics/methods PMC - PMC5777204 EDAT- 2017/10/14 06:00 MHDA- 2019/07/25 06:00 PMCR- 2018/01/01 CRDT- 2017/10/14 06:00 PHST- 2017/06/22 00:00 [received] PHST- 2017/10/04 00:00 [accepted] PHST- 2017/10/14 06:00 [pubmed] PHST- 2019/07/25 06:00 [medline] PHST- 2017/10/14 06:00 [entrez] PHST- 2018/01/01 00:00 [pmc-release] AID - haematol.2017.175083 [pii] AID - 1030172 [pii] AID - 10.3324/haematol.2017.175083 [doi] PST - ppublish SO - Haematologica. 2018 Jan;103(1):172-178. doi: 10.3324/haematol.2017.175083. Epub 2017 Oct 12.