title: Hypochlorous acid: a natural adjuvant that facilitates antigen processing, cross-priming, and the induction of adaptive immunity.
abstract: The production of hypochlorous acid (HOCl) is a characteristic of granulocyte activation, a hallmark of the early phase of innate immune responses. In this study, we show that, in addition to its well-established role as a microbicide, HOCl can act as a natural adjuvant of adaptive immunity. HOCl enhances the T cell responses to the model Ag OVA, facilitating the processing and presentation of this protein via the class II MHC pathway. HOCl modification also enhances cross-presentation of the tumor Ag tyrosinase-related protein 2 via class I MHC. The adjuvant effects of HOCl are independent of TLR signaling. The enhanced presentation of HOCl-modified OVA is mediated via modification of the N-linked carbohydrate side chain rather than formation of protein aldehydes or chloramines. HOCl-modified OVA is taken up more efficiently by APCs and is degraded more efficiently by proteinases. Atomic force microscopy demonstrated that enhanced uptake is mediated via specific receptor binding, one candidate for which is the scavenger receptor lectin-like oxidized low-density lipoprotein receptor, which shows enhanced binding to chlorinated OVA. A function of HOCl is therefore to target glycoprotein Ags to scavenger receptors on the APC surface. This additional mechanism linking innate and adaptive immunity suggests novel strategies to enhance immunity to vaccines.
authors.affiliation: Division of Infection and Immunity, University College London, London, United Kingdom.
authors.forename: Zofia M
authors.initials: ZM
authors.lastname: Prokopowicz
authors.forename: Frederick
authors.initials: F
authors.lastname: Arce
authors.forename: Rafal
authors.initials: R
authors.lastname: Biedroń
authors.forename: Cheryl L-L
authors.initials: CL
authors.lastname: Chiang
authors.forename: Marta
authors.initials: M
authors.lastname: Ciszek
authors.forename: David R
authors.initials: DR
authors.lastname: Katz
authors.forename: Maria
authors.initials: M
authors.lastname: Nowakowska
authors.forename: Szczepan
authors.initials: S
authors.lastname: Zapotoczny
authors.forename: Janusz
authors.initials: J
authors.lastname: Marcinkiewicz
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Chain
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D000938:Antigen-Presenting Cells / Q000276:immunology; D045142:Cross-Priming / Q000187:drug effects; D006098:Granulocytes; D000949:Histocompatibility Antigens Class II; D006997:Hypochlorous Acid / Q000494:pharmacology*; D007113:Immunity, Innate; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D011973:Receptors, LDL / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000949:Histocompatibility Antigens Class II; D011973:Receptors, LDL; D006997:Hypochlorous Acid; D010047:Ovalbumin