1. Human Leukocyte Antigen–DO Regulates Surface Presentation of Human Leukocyte Antigen Class II–Restricted Antigens on B Cell Malignancies.
- Author
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Kremer, Anita N., van der Meijden, Edith D., Honders, M. Willy, Pont, Margot J., Goeman, Jelle J., Falkenburg, J.H. Frederik, and Griffioen, Marieke
- Subjects
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HLA histocompatibility antigens , *BLOOD diseases , *CD4 antigen , *T cells , *INFLAMMATION , *LYMPHOCYTIC leukemia , *THERAPEUTICS - Abstract
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. [Copyright &y& Elsevier]
- Published
- 2014
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