Enhanced immunogenicity of aldehyde-bearing antigens: a possible link between innate and adaptive immunity

Allison, Michael; Fearon, Douglas T.

doi:10.1002/1521-4141(200010)30:10<2881::aid-immu2881>3.0.co;2-9

Cited by 74 publications

(52 citation statements)

References 34 publications

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“…This reaction has been extensively used to attach molecules to carrier proteins, to degly-cosylate glycoproteins, and also to stabilize protein structures [19][20][21][22]. In addition, it has been demonstrated that the introduction of aldehydes into OVA by the oxidation of their oligo-saccharides with sodium periodate enhances their immunogenicity [23].…”

Section: Introductionmentioning

confidence: 64%

Enhanced structural stability of Concholepas hemocyanin increases its immunogenicity and maintains its non‐specific immunostimulatory effects

et al. 2012

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Hemocyanins, which boost the immune system of mammals, have been used as carrieradjuvants to promote Ab production against haptens and peptides, as immunostimulants during therapy for bladder carcinoma and as a component in therapeutic vaccines for cancer. These biomedical applications have led to growing interest in obtaining hemocyanins with high immunogenicity. Here, we study the immunological properties of a modified oxidized Concholepas concholepas hemocyanin (Ox-CCH) obtained by the oxidation of its carbohydrates using sodium periodate. We assessed the internalization of Ox-CCH into DCs and its immunogenicity and antitumor effects. Transmission electron microscopy showed no changes in Ox-CCH quaternary structure with respect to native CCH, although proteolytic treatment followed by SDS-PAGE analysis demonstrated that Schiff bases were formed. Interestingly, DCs internalized Ox-CCH faster than CCH, mainly through macropinocytosis. During this process, Ox-CCH remained inside endosome-like structures for a longer period. Mouse immunization experiments demonstrated that Ox-CCH is more immunogenic and a better carrier than CCH. Moreover, Ox-CCH showed a significant antitumor effect in the B16F10 melanoma model similar to that produced by CCH, inducing IFN-γ secretion. Together, these data demonstrate that the aldehydes formed by the periodate oxidation of sugar moieties stabilizes the CCH structure, increasing its adjuvant/immunostimulatory carrier effects.

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Section: Introductionmentioning

confidence: 64%

Enhanced structural stability of Concholepas hemocyanin increases its immunogenicity and maintains its non‐specific immunostimulatory effects

et al. 2012

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“…Our previous experiments showed that oxidation of SK-OV-3 cells with 60 Amol/L HOCl induced >99% tumor cell death (14). Dendritic cells (2 Â 10 6 ) were therefore pulsed with 2 Â 10 6 60 Amol/L HOCl-oxidized SK-OV-3 cells (prepared as described in ref.…”

Section: Methodsmentioning

confidence: 99%

Oxidation of Ovarian Epithelial Cancer Cells by Hypochlorous Acid Enhances Immunogenicity and Stimulates T Cells that Recognize Autologous Primary Tumor

Chiang

Ledermann²,

Aitkens

et al. 2008

Clinical Cancer Research

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Purpose: Hypochlorous acid, a product of neutrophil myeloperoxidase, is a powerful enhancer of antigen processing and presentation. In this study, we examine whether ovarian epithelial cells (SK-OV-3) exposed to hypochlorous acid can stimulateTcells from patients with ovarian epithelial cancer that recognize common tumor antigens as well as autologous tumor. Experimental Design: Tcells from human leukocyte antigen (HLA)-A2 + and HLA-A2 -patients or healthy controls were stimulated with autologous dendritic cells cocultured with the generic ovarian tumor line SK-OV-3, previously exposed to hypochlorous acid. Results: Hypochlorous acid^treated SK-OV-3 cells drove expansion of CD8 + Tcells from HLA-A2 + individuals, which recognized the HLA-A2^restricted tumor antigen epitopes of HER-2/neu (E75 and GP2) and MUC1 (M1.1and M1.2). Up to 4.1% of theTcells were positive for the HER-2/ neu KIFGSLAFL epitope using pentamer staining. Dendritic cells loaded with oxidized SK-OV-3 cells and further matured with CD40 agonistic antibody or monophosphoryl lipid A additionally induced CD4 + class II^restricted responses. Critically, T cells stimulated with mature oxidized SK-OV-3 (but not a control oxidized melanoma cell line) directly recognized autologous tumor cells isolated from patient ascites. Conclusions: Immunization with mature dendritic cells loaded with a generic oxidized tumor cell line stimulates a polyclonal antitumor response that recognizes autologous tumor. These findings suggest a new immunotherapeutic strategy to extend remission in ovarian cancer.

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“…The use of the Schiff base-forming agent tucaresol, in addition, during immunization with protein antigen increased T cell dependent immune response. Direct modification of protein antigen has been shown to be required for the enhancement of the immune response [6,[9][10][11][12].…”

Section: Oxidation and Immune Responsementioning

confidence: 99%

Autoimmunity and oxidatively modified autoantigens

Kurien

Scofield

2008

Autoimmunity Reviews

240

194

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Oxidative damage mediated by reactive oxygen species results in the generation of deleterious byproducts. The oxidation process itself and the proteins modified by these molecules are important mediators of cell toxicity and disease pathogenesis. Aldehydic products, mainly the 4-hydroxy-2-alkenals, form adducts with proteins and make them highly immunogenic. Proteins modified in this manner have been shown to induce pathogenic antibodies in a variety of diseases including systemic lupus erythematosus (SLE), alcoholic liver disease, diabetes mellitus (DM) and rheumatoid arthritis (RA). 8-oxodeoxyguanine (oxidatively modified DNA) and low density lipoproteins (LDL) occur in SLE, a disease in which premature atherosclerosis is a serious problem. In addition, immunization with 4-hydroxy-2-nonenal (HNE) modified 60 kD Ro autoantigen induces an accelerated epitope spreading in an animal model of SLE. Advanced glycation end product (AGE) pentosidine and AGE modified IgG have been shown to correlate with RA disease activity. Oxidatively modified glutamic acid decarboxylase is important in type 1 DM, while autoantibodies against oxidized LDL are prevalent in Behcet's disease. The fragmentation of scleroderma specific autoantigens occurs as a result of oxidative modification and is thought to be responsible for the production of autoantibodies through the release of cryptic epitopes. The administration of antioxidants is a viable untried alternative for preventing or ameliorating autoimmune disease, particularly on account of the overwhelming evidence for the involvement of oxidative damage in autoimmunity. However, this should be viewed in the light of disappointing results obtained with the use of antioxidants in cardiovascular disease. Keywordslupus; autoimmunity; epitopes; autoantibodies; antigens Free radicalsReactive oxygen species (ROS) are oxygen-based molecules possessing high chemical reactivity. These include free radicals (superoxide and hydroxyl radicals) and non-radical species (hydrogen peroxide) which can be produced even at basal conditions by a number of ways. Free radicals are active species containing atoms or molecules with one or more unpaired electrons occupying an outer orbital. They can arise either by the univalent pathway of oxygen

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Enhanced immunogenicity of aldehyde-bearing antigens: a possible link between innate and adaptive immunity

Cited by 74 publications

References 34 publications

Enhanced structural stability of Concholepas hemocyanin increases its immunogenicity and maintains its non‐specific immunostimulatory effects

Enhanced structural stability of Concholepas hemocyanin increases its immunogenicity and maintains its non‐specific immunostimulatory effects

Oxidation of Ovarian Epithelial Cancer Cells by Hypochlorous Acid Enhances Immunogenicity and Stimulates T Cells that Recognize Autologous Primary Tumor

Autoimmunity and oxidatively modified autoantigens

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