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https://hdl.handle.net/2440/124967
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Type: | Journal article |
Title: | The dendritic cell receptor Clec9A binds damaged cells via exposed actin filaments |
Author: | Zhang, J.G. Czabotar, P.E. Policheni, A.N. Caminschi, I. San Wan, S. Kitsoulis, S. Tullett, K.M. Robin, A.Y. Brammananth, R. van Delft, M.F. Lu, J. O'Reilly, L.A. Josefsson, E.C. Kile, B.T. Chin, W.J. Mintern, J.D. Olshina, M.A. Wong, W. Baum, J. Wright, M.D. et al. |
Citation: | Immunity, 2012; 36(4):646-657 |
Publisher: | CellL Press |
Issue Date: | 2012 |
ISSN: | 1074-7613 1097-4180 |
Statement of Responsibility: | Jian-Guo Zhang, Peter E. Czabotar, Antonia N. Policheni, Nicos A. Nicola, Ken Shortman, Mireille H. Lahoud |
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. |
Keywords: | Dendritic Cells |
Rights: | ©2012 Elsevier Inc. |
DOI: | 10.1016/j.immuni.2012.03.009 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/454465 http://purl.org/au-research/grants/nhmrc/461219 http://purl.org/au-research/grants/nhmrc/461221 http://purl.org/au-research/grants/nhmrc/575546 http://purl.org/au-research/grants/nhmrc/1009145 ARC NHMRC |
Published version: | http://dx.doi.org/10.1016/j.immuni.2012.03.009 |
Appears in Collections: | Aurora harvest 8 Environment Institute publications |
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