The dendritic cell receptor Clec9A binds damaged cells via exposed actin filaments

Jian-Guo Zhang, Peter E. Czabotar, Antonia N. Policheni, Irina Caminschi, Soo San Wan, Susie Kitsoulis, Kirsteen M. Tullett, Adeline Y. Robin, Rajini Brammananth, Mark F. van Delft, Jinhua Lu, Lorraine A. O'Reilly, Emma C. Josefsson, Benjamin T. Kile, Wei Jin Chin, Justine D. Mintern, Maya A. Olshina, Wilson Wong, Jake Baum, Mark D. Wright & 7 others David C.S. Huang, Narla Mohandas, Ross L. Coppel, Peter M. Colman, Nicos A. Nicola, Ken Shortman, Mireille H. Lahoud

Research output: Contribution to journalArticleResearchpeer-review

162 Citations (Scopus)

Abstract

The immune system must distinguish viable cells from cells damaged by physical and infective processes. The damaged cell-recognition molecule Clec9A is expressed on the surface of the mouse and human dendritic cell subsets specialized for the uptake and processing of material from dead cells. Clec9A recognizes a conserved component within nucleated and nonnucleated cells, exposed when cell membranes are damaged. We have identified this Clec9A ligand as a filamentous form of actin in association with particular actin-binding domains of cytoskeletal proteins. We have determined the crystal structure of the human CLEC9A C-type lectin domain and propose a functional dimeric structure with conserved tryptophans in the ligand recognition site. Mutation of these residues ablated CLEC9A binding to damaged cells and to the isolated ligand complexes. We propose that Clec9A provides targeted recruitment of the adaptive immune system during infection and can also be utilized to enhance immune responses generated by vaccines.
Original languageEnglish
Pages (from-to)646-657
Number of pages12
JournalImmunity
Volume36
Issue number4
DOIs
Publication statusPublished - 2012

Cite this

Zhang, Jian-Guo ; Czabotar, Peter E. ; Policheni, Antonia N. ; Caminschi, Irina ; Wan, Soo San ; Kitsoulis, Susie ; Tullett, Kirsteen M. ; Robin, Adeline Y. ; Brammananth, Rajini ; van Delft, Mark F. ; Lu, Jinhua ; O'Reilly, Lorraine A. ; Josefsson, Emma C. ; Kile, Benjamin T. ; Chin, Wei Jin ; Mintern, Justine D. ; Olshina, Maya A. ; Wong, Wilson ; Baum, Jake ; Wright, Mark D. ; Huang, David C.S. ; Mohandas, Narla ; Coppel, Ross L. ; Colman, Peter M. ; Nicola, Nicos A. ; Shortman, Ken ; Lahoud, Mireille H. / The dendritic cell receptor Clec9A binds damaged cells via exposed actin filaments. In: Immunity. 2012 ; Vol. 36, No. 4. pp. 646-657.
@article{26655d571e20446caea18241949b070c,
title = "The dendritic cell receptor Clec9A binds damaged cells via exposed actin filaments",
abstract = "The immune system must distinguish viable cells from cells damaged by physical and infective processes. The damaged cell-recognition molecule Clec9A is expressed on the surface of the mouse and human dendritic cell subsets specialized for the uptake and processing of material from dead cells. Clec9A recognizes a conserved component within nucleated and nonnucleated cells, exposed when cell membranes are damaged. We have identified this Clec9A ligand as a filamentous form of actin in association with particular actin-binding domains of cytoskeletal proteins. We have determined the crystal structure of the human CLEC9A C-type lectin domain and propose a functional dimeric structure with conserved tryptophans in the ligand recognition site. Mutation of these residues ablated CLEC9A binding to damaged cells and to the isolated ligand complexes. We propose that Clec9A provides targeted recruitment of the adaptive immune system during infection and can also be utilized to enhance immune responses generated by vaccines.",
author = "Jian-Guo Zhang and Czabotar, {Peter E.} and Policheni, {Antonia N.} and Irina Caminschi and Wan, {Soo San} and Susie Kitsoulis and Tullett, {Kirsteen M.} and Robin, {Adeline Y.} and Rajini Brammananth and {van Delft}, {Mark F.} and Jinhua Lu and O'Reilly, {Lorraine A.} and Josefsson, {Emma C.} and Kile, {Benjamin T.} and Chin, {Wei Jin} and Mintern, {Justine D.} and Olshina, {Maya A.} and Wilson Wong and Jake Baum and Wright, {Mark D.} and Huang, {David C.S.} and Narla Mohandas and Coppel, {Ross L.} and Colman, {Peter M.} and Nicola, {Nicos A.} and Ken Shortman and Lahoud, {Mireille H.}",
year = "2012",
doi = "10.1016/j.immuni.2012.03.009",
language = "English",
volume = "36",
pages = "646--657",
journal = "Immunity",
issn = "1074-7613",
publisher = "Elsevier",
number = "4",

}

Zhang, J-G, Czabotar, PE, Policheni, AN, Caminschi, I, Wan, SS, Kitsoulis, S, Tullett, KM, Robin, AY, Brammananth, R, van Delft, MF, Lu, J, O'Reilly, LA, Josefsson, EC, Kile, BT, Chin, WJ, Mintern, JD, Olshina, MA, Wong, W, Baum, J, Wright, MD, Huang, DCS, Mohandas, N, Coppel, RL, Colman, PM, Nicola, NA, Shortman, K & Lahoud, MH 2012, 'The dendritic cell receptor Clec9A binds damaged cells via exposed actin filaments', Immunity, vol. 36, no. 4, pp. 646-657. https://doi.org/10.1016/j.immuni.2012.03.009

The dendritic cell receptor Clec9A binds damaged cells via exposed actin filaments. / Zhang, Jian-Guo; Czabotar, Peter E.; Policheni, Antonia N.; Caminschi, Irina; Wan, Soo San; Kitsoulis, Susie; Tullett, Kirsteen M.; Robin, Adeline Y.; Brammananth, Rajini; van Delft, Mark F.; Lu, Jinhua; O'Reilly, Lorraine A.; Josefsson, Emma C.; Kile, Benjamin T.; Chin, Wei Jin; Mintern, Justine D.; Olshina, Maya A.; Wong, Wilson; Baum, Jake; Wright, Mark D.; Huang, David C.S.; Mohandas, Narla; Coppel, Ross L.; Colman, Peter M.; Nicola, Nicos A.; Shortman, Ken; Lahoud, Mireille H.

In: Immunity, Vol. 36, No. 4, 2012, p. 646-657.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The dendritic cell receptor Clec9A binds damaged cells via exposed actin filaments

AU - Zhang, Jian-Guo

AU - Czabotar, Peter E.

AU - Policheni, Antonia N.

AU - Caminschi, Irina

AU - Wan, Soo San

AU - Kitsoulis, Susie

AU - Tullett, Kirsteen M.

AU - Robin, Adeline Y.

AU - Brammananth, Rajini

AU - van Delft, Mark F.

AU - Lu, Jinhua

AU - O'Reilly, Lorraine A.

AU - Josefsson, Emma C.

AU - Kile, Benjamin T.

AU - Chin, Wei Jin

AU - Mintern, Justine D.

AU - Olshina, Maya A.

AU - Wong, Wilson

AU - Baum, Jake

AU - Wright, Mark D.

AU - Huang, David C.S.

AU - Mohandas, Narla

AU - Coppel, Ross L.

AU - Colman, Peter M.

AU - Nicola, Nicos A.

AU - Shortman, Ken

AU - Lahoud, Mireille H.

PY - 2012

Y1 - 2012

N2 - The immune system must distinguish viable cells from cells damaged by physical and infective processes. The damaged cell-recognition molecule Clec9A is expressed on the surface of the mouse and human dendritic cell subsets specialized for the uptake and processing of material from dead cells. Clec9A recognizes a conserved component within nucleated and nonnucleated cells, exposed when cell membranes are damaged. We have identified this Clec9A ligand as a filamentous form of actin in association with particular actin-binding domains of cytoskeletal proteins. We have determined the crystal structure of the human CLEC9A C-type lectin domain and propose a functional dimeric structure with conserved tryptophans in the ligand recognition site. Mutation of these residues ablated CLEC9A binding to damaged cells and to the isolated ligand complexes. We propose that Clec9A provides targeted recruitment of the adaptive immune system during infection and can also be utilized to enhance immune responses generated by vaccines.

AB - The immune system must distinguish viable cells from cells damaged by physical and infective processes. The damaged cell-recognition molecule Clec9A is expressed on the surface of the mouse and human dendritic cell subsets specialized for the uptake and processing of material from dead cells. Clec9A recognizes a conserved component within nucleated and nonnucleated cells, exposed when cell membranes are damaged. We have identified this Clec9A ligand as a filamentous form of actin in association with particular actin-binding domains of cytoskeletal proteins. We have determined the crystal structure of the human CLEC9A C-type lectin domain and propose a functional dimeric structure with conserved tryptophans in the ligand recognition site. Mutation of these residues ablated CLEC9A binding to damaged cells and to the isolated ligand complexes. We propose that Clec9A provides targeted recruitment of the adaptive immune system during infection and can also be utilized to enhance immune responses generated by vaccines.

UR - http://www.sciencedirect.com/science/article/pii/S1074761312001276

U2 - 10.1016/j.immuni.2012.03.009

DO - 10.1016/j.immuni.2012.03.009

M3 - Article

VL - 36

SP - 646

EP - 657

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 4

ER -