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      Direct Delivery of Antigens to Dendritic Cells via Antibodies Specific for Endocytic Receptors as a Promising Strategy for Future Therapies

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          Abstract

          Dendritic cells (DCs) are the most potent professional antigen presenting cells and are therefore indispensable for the control of immunity. The technique of antibody mediated antigen targeting to DC subsets has been the basis of intense research for more than a decade. Many murine studies have utilized this approach of antigen delivery to various kinds of endocytic receptors of DCs both in vitro and in vivo. Today, it is widely accepted that different DC subsets are important for the induction of select immune responses. Nevertheless, many questions still remain to be answered, such as the actual influence of the targeted receptor on the initiation of the immune response to the delivered antigen. Further efforts to better understand the induction of antigen-specific immune responses will support the transfer of this knowledge into novel treatment strategies for human diseases. In this review, we will discuss the state-of-the-art aspects of the basic principles of antibody mediated antigen targeting approaches. A table will also provide a broad overview of the latest studies using antigen targeting including addressed DC subset, targeted receptors, outcome, and applied coupling techniques.

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          Most cited references243

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          Taking dendritic cells into medicine.

          Dendritic cells (DCs) orchestrate a repertoire of immune responses that bring about resistance to infection and silencing or tolerance to self. In the settings of infection and cancer, microbes and tumours can exploit DCs to evade immunity, but DCs also can generate resistance, a capacity that is readily enhanced with DC-targeted vaccines. During allergy, autoimmunity and transplant rejection, DCs instigate unwanted responses that cause disease, but, again, DCs can be harnessed to silence these conditions with novel therapies. Here we present some medical implications of DC biology that account for illness and provide opportunities for prevention and therapy.
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            Differential antigen processing by dendritic cell subsets in vivo.

            Dendritic cells (DCs) process and present self and foreign antigens to induce tolerance or immunity. In vitro models suggest that induction of immunity is controlled by regulating the presentation of antigen, but little is known about how DCs control antigen presentation in vivo. To examine antigen processing and presentation in vivo, we specifically targeted antigens to two major subsets of DCs by using chimeric monoclonal antibodies. Unlike CD8+ DCs that express the cell surface protein CD205, CD8- DCs, which are positive for the 33D1 antigen, are specialized for presentation on major histocompatibility complex (MHC) class II. This difference in antigen processing is intrinsic to the DC subsets and is associated with increased expression of proteins involved in MHC processing.
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              Signalling through C-type lectin receptors: shaping immune responses

              Key Points Crosstalk between pattern recognition receptors (PRRs) expressed by dendritic cells orchestrates T helper (TH) cell differentiation through the induction of specific cytokine expression profiles, tailored to invading pathogens. C-type lectin receptors (CLRs) have an important role in orchestrating the induction of signalling pathways that regulate adaptive immune responses. CLRs can control adaptive immunity at various levels by inducing signalling on their own, through crosstalk with other PRRs or by inducing carbohydrate-specific signalling pathways. DC-specific ICAM3-grabbing non-integrin (DC-SIGN) interacts with mannose-carrying pathogens including Mycobacterium tuberculosis, HIV-1, measles virus and Candida albicans to activate the serine/threonine protein kinase RAF1. RAF1 signalling leads to the acetylation of Toll-like receptor (TLR)-activated nuclear factor-κB (NF-κB) subunit p65 and affects cytokine expression, such as inducing the upregulation of interleukin-10 (IL-10). DC-associated C-type lectin 1 (dectin 1) triggering by a broad range of fungal pathogens, such as C. albicans, Aspergillus fumigatus and Pneumocystis carinii, results in protective antifungal immunity through the crosstalk of two independent signalling pathways — one through spleen tyrosine kinase (SYK) and one through RAF1 — that are essential for the expression of TH1 and TH17 cell polarizing cytokines. Crosstalk between the SYK and RAF1 pathways is both synergistic and antagonizing to fine-tune NF-κB activity: although Ser276 phosphorylation of p65 leads to enhanced transcriptional activity of p65 itself through acetylation, it also inhibits the transcriptional activity of the NF-κB subunit RELB by sequestering it in p65–RELB dimers, which are transcriptionally inactive. The diversity in CLR-mediated signalling provides some major challenges for the researches to elucidate and manipulate the signalling properties of this exciting family of receptors. However, the recent advances strongly support the use of CLR targeting vaccination strategies using dendritic cells to induce or redirect adaptive immune responses as well as improve antigen delivery.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Vaccines (Basel)
                Vaccines (Basel)
                vaccines
                Vaccines
                MDPI
                2076-393X
                28 March 2016
                June 2016
                : 4
                : 2
                : 8
                Affiliations
                [1 ]Laboratory of DC-Biology, Department of Dermatology, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital Erlangen, Hartmannstr. 14, Erlangen 91052, Germany; christian.lehmann@ 123456uk-erlangen.de (C.H.K.L.); lukas.heger@ 123456uk-erlangen.de (L.H.); gordon.heidkamp@ 123456uk-erlangen.de (G.F.H.); baranska@ 123456ciml.univ-mrs.fr (A.B.); jennifer.lühr@ 123456uk-erlangen.de (J.J.L.); alana.hoffmann@ 123456uk-erlangen.de (A.H.)
                [2 ]Centre d’Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM-CNRS, Marseille-Luminy 13288, France
                Author notes
                [* ]Correspondence: diana.dudziak@ 123456uk-erlangen.de ; Tel.: +49-9131-85-39346; Fax: +49-9131-85-39347
                Article
                vaccines-04-00008
                10.3390/vaccines4020008
                4931625
                27043640
                1ea9a3ad-6b0f-494b-ae47-202da9a68f85
                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 19 February 2016
                : 18 March 2016
                Categories
                Review

                antigen targeting,antigen targeting antibodies,cancer,clr,dc,dcir,dec205,dendritic cell subsets,modc,vaccine

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