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DNGR-1, an F-Actin-Binding C-Type Lectin Receptor Involved in Cross-Presentation of Dead Cell-Associated Antigens by Dendritic Cells

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C-Type Lectin Receptors in Immunity

Abstract

DNGR-1 (also known as CLEC9A) is a C-type lectin homodimeric innate immune receptor that detects the presence of dead cells (Sancho et al. 2009). In both mouse and Man, DNGR-1 is specifically expressed at high levels by dendritic cells (DCs), in particular the XCR1+ ‘CD8α+-like’ subtype that excels in the ability to cross-present cell-associated antigens to CD8+ T cells (Caminschi et al. 2008; Huysamen et al. 2008; Poulin et al. 2010, 2012; Sancho et al. 2008). DNGR-1 plays a key role in the latter process. The receptor is found both at the DC surface and within endosomes, with its ligand-binding domains facing the exterior milieu or the endosomal lumen. This topology allows for effective surveillance of cell corpses with which DCs come into contact, as well as internalised dead cell debris. DNGR-1 signalling, in part via Syk, in response to engagement by ligand, acts to delay endosomal maturation and slow cargo degradation, ensuring the preservation of dead cell-associated antigens (Iborra et al. 2012; Sancho et al. 2009; Zelenay et al. 2012). Whilst the actual mechanism underlying the regulation of cross-presentation of antigens from cellular corpses by DNGR-1 remains a mystery, progress has been made in identifying the ligand. This turns out to be F-actin, an abundant intracellular component that is inaccessible in intact cells and whose exposure therefore serves as a damage-associated molecular pattern (DAMP) (Ahrens et al. 2012; Zhang et al. 2012). The recently solved structure of the DNGR-1: F-actin complex shows that each ligand-binding domain of the receptor nests in the groove between two F-actin protofilaments and contacts three actin subunits. The structure clearly explains specificity of the receptor for F-actin and sheds light into the mode of binding and its biophysical characteristics (Hanč et al. 2015). Here, we review the properties and biology of DNGR-1 and the importance of cytoskeletal recognition in innate immune detection of cell damage.

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Authors and Affiliations

  1. Immunobiology Laboratory, Lincoln’s Inn Fields Laboratory, The Francis Crick Institute, 44 Lincoln’s Inn Fields, London, WC2A 3LY, UK

    Pavel Hanč, Santiago Zelenay, Janneke van Blijswijk & Caetano Reis e Sousa

  2. Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain

    Salvador Iborra & David Sancho

  3. Cancer Inflammation and Immunity Laboratory, Cancer Research UK Manchester Institute, The University of Manchester, Wilmslow Road, Manchester, M20 4BX, UK

    Santiago Zelenay

Authors
  1. Pavel Hanč
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  2. Salvador Iborra
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  3. Santiago Zelenay
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  4. Janneke van Blijswijk
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  5. David Sancho
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  6. Caetano Reis e Sousa
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Corresponding author

Correspondence to Caetano Reis e Sousa .

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Editors and Affiliations

  1. Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan

    Sho Yamasaki

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Hanč, P., Iborra, S., Zelenay, S., van Blijswijk, J., Sancho, D., Reis e Sousa, C. (2016). DNGR-1, an F-Actin-Binding C-Type Lectin Receptor Involved in Cross-Presentation of Dead Cell-Associated Antigens by Dendritic Cells. In: Yamasaki, S. (eds) C-Type Lectin Receptors in Immunity. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56015-9_5

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