title: Human leukocyte antigen-DO regulates surface presentation of human leukocyte antigen class II-restricted antigens on B cell malignancies.
abstract: Hematological malignancies often express surface HLA class II, making them attractive targets for CD4+ T cell therapy. We previously demonstrated that HLA class II ligands can be divided into DM-resistant and DM-sensitive antigens. In contrast to presentation of DM-resistant antigens, presentation of DM-sensitive antigens is suppressed by HLA-DM but can be rescued by HLA-DO. We also showed that HLA-DO expression remains low in nonhematopoietic cells under inflammatory conditions, suggesting that DM-sensitive antigens may be ideal T cell targets with a low risk for graft-versus-host disease. Here, we demonstrated that B cell malignancies often express HLA-DO and that levels are in particular high in chronic lymphocytic leukemia. Moreover, we showed that surface presentation of DM-sensitive antigens is regulated by HLA-DO, and that DM-sensitive antigens are relevant T cell targets for B cell malignancies and, especially, chronic lymphocytic leukemia. These data open the perspective to target HLA class II ligands with specific processing and presentation behavior for CD4+ T cell therapy of hematological malignancies.
authors: Department of Hematology, Leiden University Medical Center, RC Leiden, The Netherlands; Department of Internal Medicine 5, Hematology and Oncology, University Hospital Erlangen, Erlangen, Germany.
authors: Anita N
authors: AN
authors: Kremer
authors: Department of Hematology, Leiden University Medical Center, RC Leiden, The Netherlands.
authors: Edith D
authors: ED
authors: van der Meijden
authors: Department of Hematology, Leiden University Medical Center, RC Leiden, The Netherlands.
authors: M Willy
authors: MW
authors: Honders
authors: Department of Hematology, Leiden University Medical Center, RC Leiden, The Netherlands.
authors: Margot J
authors: MJ
authors: Pont
authors: Department of Medical Statistics, Leiden University Medical Center, RC Leiden, The Netherlands.
authors: Jelle J
authors: JJ
authors: Goeman
authors: Department of Hematology, Leiden University Medical Center, RC Leiden, The Netherlands.
authors: J H Frederik
authors: JH
authors: Falkenburg
authors: Department of Hematology, Leiden University Medical Center, RC Leiden, The Netherlands. Electronic address: M.Griffioen@lumc.nl.
authors: Marieke
authors: M
authors: Griffioen
mesh_terms: D017951:Antigen Presentation / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000276:immunology*; D006681:HLA-D Antigens / Q000235:genetics / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D061251:Primary Cell Culture
chemical_list: D006681:HLA-D Antigens; C084245:HLA-DM antigens; C046148:HLA-DO antigens
keywords: Allogeneic stem cell transplantation; CD4+ T lymphocytes; Graft-versus-leukemia; Human leukocyte antigen class II; Leukemia; T lymphocytes