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+ Tcell 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 Tcell targets with a low risk for graft-versus-host disease. Here, we demonstrated that Bcell 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 Tcell targets for Bcell 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+ Tcell therapy of hematological malignancies. © 2014 American Society for Blood and Marrow Transplantation.