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The Journal of Immunology, 2008, 181, 3212-3220
Copyright © 2008 by The American Association of Immunologists, Inc.

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The Relative Efficiency of Acquisition of MHC:Peptide Complexes and Cross-Presentation Depends on Dendritic Cell Type1

Lesley Ann Smyth*, Nicola Harker{dagger}, Wayne Turnbull{ddagger}, Haytham El-Doueik{ddagger}, Linda Klavinskis{ddagger}, Dimitris Kioussis{dagger}, Giovanna Lombardi* and Robert Lechler2,*

* Department of Nephrology and Transplantation, King’s College London, School of Medicine, Guy’s Hospital, {dagger} National Institute for Medical Research, Division of Molecular Immunology, {ddagger} Peter Gorer Department of Immunobiology, King’s College London, School of Medicine, Guy’s Hospital, London, United Kingdom

Intercellular exchange of MHC molecules has been reported between many cells, including professional and nonprofessional APCs. This phenomenon may contribute to T cell immunity to pathogens. In this study, we addressed whether the transfer of MHC class I:peptide complexes between cells plays a role in T cell responses and compare this to conventional cross-presentation. We observed that dsRNA-matured bone marrow-derived dendritic cells (BMDCs) acquired peptide:MHC complexes from other BMDCs either pulsed with OVA257–264 peptide, soluble OVA, or infected with a recombinant adenovirus expressing OVA. In addition, BMDCs were capable of acquiring MHC:peptide complexes from epithelial cells. Spleen-derived CD8{alpha}+ and CD8{alpha} dendritic cells (DCs) also acquired MHC:peptide complexes from BMDCs pulsed with OVA257–264 peptide. However, the efficiency of acquisition by these ex vivo derived DCs is much lower than acquisition by BMDC. In all cases, the acquired MHC:peptide complexes were functional in that they induced Ag-specific CD8+ T cell proliferation. The efficiency of MHC transfer was compared with cross-presentation for splenic CD8{alpha}+ and CD8{alpha} as well as BMDCs. CD8{alpha}+ DCs were more efficient at inducing T cell proliferation when they acquired Ag via cross-presentation, the opposite was observed for BMDCs and splenic CD8{alpha} DCs. We conclude from these observations that the relative efficiency of MHC transfer vs cross-presentation differs markedly between different DC subsets.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by a grant from the British Heart Foundation.

2 Address correspondence and reprint requests to Dr. Robert Lechler, Immunoregulation Laboratories, 5th Floor Thomas Guys House, King’s College London, Guy’s Campus, London SE1 9RT, U.K. E-mail address: robert.lechler{at}kcl.ac.uk

3 Abbreviations used in this paper: DC, dendritic cell; BMDC, bone marrow-derived DC; rAd, recombinant adenovirus.




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C. Qu, V. A. Nguyen, M. Merad, and G. J. Randolph
MHC Class I/Peptide Transfer between Dendritic Cells Overcomes Poor Cross-Presentation by Monocyte-Derived APCs That Engulf Dying Cells
J. Immunol., March 15, 2009; 182(6): 3650 - 3659.
[Abstract] [Full Text] [PDF]




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