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23rd International Lectin Meeting (Interlec-23)

C-type lectins on dendritic cells: key modulators for the induction of immune responses

Yvette van Kooyk
Biochemical Society Transactions Dec 01, 2008, 36 (6) 1478-1481; DOI: 10.1042/BST0361478
Yvette van Kooyk
Department of Molecular Cell Biology and Immunology VU University Medical Center Amsterdam, v.d. Boechorststraat 7, 1081 BT Amsterdam, The Netherlands
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Abstract

DCs (dendritic cells) are specialized in the recognition of pathogens and play a pivotal role in the control of immune responses. DCs are also important for homoeostatic control, recognizing self-antigens and tolerizing the tissue environment. The nature of the antigen recognized tilts the balance towards immunity or tolerance. CLRs (C-type lectin receptors) expressed by DC are involved in the recognition and capture of many glycosylated self-antigens and pathogens. It is now becoming clear that these CLRs may not only serve as antigen receptors allowing internalization and antigen presentation, but also function in the recognition of glycosylated self-antigens, and as adhesion and/or signalling molecules. The expression of C-type lectins is very sensitive to maturation stimuli, leading to down-regulation as DCs mature. CLRs such as DC-SIGN (DC-specific intracellular adhesion molecule-3 grabbing non-integrin) recognizes high-mannose-containing structures and Lewis antigens (Lex, Ley, Leb and Lea), whereas the CLR MGL (macrophage galactose/N-acetylgalactosamine-specific C-type lectin) recognizes GalNAc. Lex, Ley and GalNAc glycan structures are often expressed on tumours. We have demonstrated that glycan modification of antigen can strongly enhance MHC class I responses and the induction of antigen-specific cytotoxic T-lymphocytes, indicating that glycosylated antigen targets C-type lectin to enhance antigen-specific T-cell responses. Moreover, these CLRs induce signalling processes in DCs and specific cytokine responses in combination with TLR (Toll-like receptor) triggering. This implies that specific C-type lectin-targeted antigens can regulate T-cell polarization. Understanding the diversity of C-type lectins being expressed on DCs as well as their carbohydrate-specific recognition profiles should promote understanding of pathogen recognition in many diseases, as well as the regulation of cellular interactions of DCs that are essential in the control of immunity.

  • carbohydrate
  • C-type lectin
  • dendritic cell
  • targeting antigen
  • Toll-like receptor

Footnotes

  • 23rd International Lectin Meeting (Interlec-23): Independent meeting held at Universities of Edinburgh and Stirling, Scotland, U.K., 11–16 July 2008. Organized and Edited by Dave Kilpatrick (Scottish National Blood Transfusion Service, National Science Laboratory, Edinburgh, U.K.).

Abbreviations: APC, antigen-presenting cell; CEA, carcinoma embryonic antigen; CLR, C-type lectin receptor; CRD, carbohydrate-recognition domain; DC, dendritic cell; DC-SIGN, DC-specific intracellular adhesion molecule-3 grabbing non-integrin; IL, interleukin; MGL, macrophage galactose/N-acetylgalactosamine-specific C-type lectin; MR, mannose receptor; MUC1, mucin 1; PRR, pattern-recognition receptor; TAA, tumour-associated antigen; TLR, Toll-like receptor; Treg, regulatory T-cell

  • © The Authors Journal compilation © 2008 Biochemical Society
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December 2008

Volume: 36 Issue: 6

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C-type lectins on dendritic cells: key modulators for the induction of immune responses
Yvette van Kooyk
Biochemical Society Transactions Dec 2008, 36 (6) 1478-1481; DOI: 10.1042/BST0361478
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C-type lectins on dendritic cells: key modulators for the induction of immune responses
Yvette van Kooyk
Biochemical Society Transactions Dec 2008, 36 (6) 1478-1481; DOI: 10.1042/BST0361478

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Keywords

carbohydrate
C-type lectin
dendritic cell
targeting antigen
Toll-like receptor

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