title: Mobilizing monocytes to cross-present circulating viral antigen in chronic infection.
abstract: Selection of antigens for therapeutic vaccination against chronic viral infections is complicated by pathogen genetic variations. We tested whether antigens present during persistent viral infections could provide a personalized antigenic reservoir for therapeutic T cell expansion in humans. We focused our study on the HBV surface antigen (HBsAg), which is present in microgram quantities in the serum of chronic HBV patients. We demonstrated by quantitative fluorescent microscopy that, out of 6 professional APC populations in the circulation, only CD14 monocytes (MNs) retained an HBsAg depot. Using TCR-redirected CD8+ T cells specific for MHC-I-restricted HBV epitopes, we showed that, despite being constantly exposed to antigen, ex vivo-isolated APCs did not constitutively activate HBV-specific CD8+ T cells. However, differentiation of HBsAg+ CD14 MNs from chronic patients to MN-derived DCs (moDCs) induced cross-presentation of the intracellular reservoir of viral antigen. We exploited this mechanism to cross-present circulating viral antigen and showed that moDCs from chronically infected patients stimulated expansion of autologous HBV-specific T cells. Thus, these data demonstrate that circulating viral antigen produced during chronic infection can serve as a personalized antigenic reservoir to activate virus-specific T cells.
authors.affiliation: Infection and Immunity Programme, Singapore Institute for Clinical Sciences, Agency for Science Technology and Research, Singapore. gehringa@slu.edu
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Gehring
authors.forename: Muzlifah
authors.initials: M
authors.lastname: Haniffa
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Kennedy
authors.forename: Zi Zong
authors.initials: ZZ
authors.lastname: Ho
authors.forename: Carolina
authors.initials: C
authors.lastname: Boni
authors.forename: Amanda
authors.initials: A
authors.lastname: Shin
authors.forename: Nasirah
authors.initials: N
authors.lastname: Banu
authors.forename: Adeline
authors.initials: A
authors.lastname: Chia
authors.forename: Seng Gee
authors.initials: SG
authors.lastname: Lim
authors.forename: Carlo
authors.initials: C
authors.lastname: Ferrari
authors.forename: Florent
authors.initials: F
authors.lastname: Ginhoux
authors.forename: Antonio
authors.initials: A
authors.lastname: Bertoletti
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D045142:Cross-Priming; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000097:blood / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000276:immunology*; D006801:Humans; D009000:Monocytes / Q000276:immunology* / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology
chemical_list: D006514:Hepatitis B Surface Antigens
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