Enhancement of immunogenic properties of ovalbumin as a result of its chlorination

Marcinkiewicz, Janusz; Chain, Benjamin M.; Olszowska, Ewa; Olszowski, S.; Zgliczyński, J.M.

doi:10.1016/0020-711x(91)90280-z

Cited by 47 publications

(36 citation statements)

References 10 publications

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“…The influence of protein chlorination on adaptive immunity, however, has received relatively little attention. The hypothesis underlying this study, based on earlier studies (34,35), was that chlorination might act as a natural adjuvant, facilitating recognition by APCs and hence enhancing the overall immune response.…”

Section: Discussionmentioning

confidence: 99%

Hypochlorous Acid: A Natural Adjuvant That Facilitates Antigen Processing, Cross-Priming, and the Induction of Adaptive Immunity

Prokopowicz

Arce

Biedroń

et al. 2009

The Journal of Immunology

297

142

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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.

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Section: Discussionmentioning

confidence: 99%

Hypochlorous Acid: A Natural Adjuvant That Facilitates Antigen Processing, Cross-Priming, and the Induction of Adaptive Immunity

Prokopowicz

Arce

Biedroń

et al. 2009

The Journal of Immunology

297

142

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“…Hypochlorous acid (HOCl), a potent oxidant produced during acute inflammation, shows strong microbicidal activity as well as ability to enhance the immunogenicity of protein antigens by several folds via oxidation both in vivo and ex vivo [35][36][37]. Proteins oxidized by HOCl are more readily taken up and processed by antigen presenting cells (APCs) and led to enhanced activation of antigen-specific T cells in vitro [38][39][40][41].…”

Section: Oxidation Of Whole Tumor Cells With Hypochlorous Acidmentioning

confidence: 99%

Adjuvants for Enhancing the Immunogenicity of Whole Tumor Cell Vaccines

Chiang

Kandalaft

Coukos

2011

International Reviews of Immunology

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Whole tumor cell lysates can serve as excellent multivalent vaccines for priming tumor-specific CD8(+) and CD4(+) T cells. Whole cell vaccines can be prepared with hypochlorous acid oxidation, UVB-irradiation and repeat cycles of freeze and thaw. One major obstacle to successful immunotherapy is breaking self-tolerance to tumor antigens. Clinically approved adjuvants, including Montanide™ ISA-51 and 720, and keyhole-limpet proteins can be used to enhance tumor cell immunogenicity by stimulating both humoral and cellular anti-tumor responses. Other potential adjuvants, such as Toll-like receptor agonists (e.g., CpG, MPLA and PolyI:C), and cytokines (e.g., granulocyte-macrophage colony stimulating factor), have also been investigated.

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“…Early work showed that HOCl oxidation lowered the threshold of ovalbumin required to stimulate both cellular and humoral immune responses. Enhanced responses were due to increased T cell responses, which, in turn, derived from improved processing and presentation (Marcinkiewicz et al 1991(Marcinkiewicz et al , 1992. Oxidation of hen egg lysozyme and bovine a-lactalbumin, either via chlorination or via performic acid, induced higher T cell activation responses when presented by macrophages (Carrasco-Marin et al 1998).…”

Section: Mpo Hocl and The Enhancement Of Adaptive Immunitymentioning

confidence: 99%

Neutrophil Myeloperoxidase: Soldier and Statesman

Prokopowicz¹,

Marcinkiewicz

Katz³

et al. 2011

Arch. Immunol. Ther. Exp.

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Myeloperoxidase (MPO) is a major protein constituent of the primary granules of vertebrate neutrophils. It catalyses the hydrogen peroxide-mediated oxidation of halide ions to hypohalous acids, especially HOCl. These reactive oxygen species can participate in a variety of secondary reactions, leading to modifications of amino acids and many types of biological macromolecules. The classic paradigm views MPO as a component of the phagocyte oxygen-dependent intracellular microbicidal system, and thus an important arm of the effector phase of innate immune responses. However, the limited immunodeficiency associated with lack of MPO in mouse and human models has challenged this paradigm. In this review we examine more recent information on the interaction between MPO, its bioreactive reaction products, and targets within the inflammatory microenvironment. We propose that two assumptions of the current model may require revisiting. First, many important targets of MPO modification are extracellular, rather than present only within the phagolysosome, such as various components of neutrophil extracellular traps. Second, we suggest that the pro-inflammatory pathological role of MPO may be a particular feature of chronic inflammation. In the physiological setting of acute neutrophil-mediated inflammation MPO may also form part of a negative feedback loop which down-regulates inflammation, limits tissue damage, and facilitates the switch from innate to adaptive immunity. This different perspective on this well-studied enzyme may usefully inform further research into its function in health and disease.

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Enhancement of immunogenic properties of ovalbumin as a result of its chlorination

Cited by 47 publications

References 10 publications

Hypochlorous Acid: A Natural Adjuvant That Facilitates Antigen Processing, Cross-Priming, and the Induction of Adaptive Immunity

Hypochlorous Acid: A Natural Adjuvant That Facilitates Antigen Processing, Cross-Priming, and the Induction of Adaptive Immunity

Adjuvants for Enhancing the Immunogenicity of Whole Tumor Cell Vaccines

Neutrophil Myeloperoxidase: Soldier and Statesman

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