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International Immunology Advance Access originally published online on June 10, 2004
International Immunology 2004 16(8):1091-1098; doi:10.1093/intimm/dxh110
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© 2004 The Japanese Society for Immunology

ORIGINAL RESEARCH PAPERS

CpG oligodeoxynucleotides enhance Fc{gamma}RI-mediated cross presentation by dendritic cells

Lisette Bevaart1, Heidi H. Van Ojik1, Amanda W. Sun2, Timothy H. Sulahian2, Jeanette H. W. Leusen1, George J. Weiner3, Jan G. J. van de Winkel1,4 and Martine J. Van Vugt1,4

1 Immunotherapy Laboratory, Department of Immunology, University Medical Center Utrecht, Lundlaan 6, Room KC02-085.2, 3584 EA, Utrecht, The Netherlands
2 Department of Physiology, Dartmouth Medical School, Lebanon, NH 03756, USA
3 The Holden Comprehensive Cancer Center and Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA
4 Genmab, Jenalaan 18d, 3584 CK, Utrecht, The Netherlands

Correspondence to: M. J. van Vugt; E-mail: M.vanvugt{at}nl.genmab.com

Dendritic cells (DC) can trigger naive CD8+ T cell responses by their capacity to cross-present exogenous antigens via the major histocompatibility complex class I pathway. The myeloid class I IgG receptor, Fc{gamma}RI (CD64), is expressed on DC, and in vivo targeting of antigens to Fc{gamma}RI induces strong humoral and cellular immune responses. We studied the capacity of human Fc{gamma}RI (hFc{gamma}RI) to facilitate DC-mediated cross presentation and T cell activation, and assessed the effect of CpG oligodeoxynucleotides on this process. We generated hFc{gamma}RI expressing immature DC from hFc{gamma}RI transgenic and immature DC from non-transgenic mice. Antigens were targeted to Fc{gamma} receptors as ovalbumin immune complexes, or selectively to hFc{gamma}RI via ovalbumin–CD64 mAb fusion proteins. Co-incubation of immature DC with CpG ODN led to markedly increased MHC class I presentation of Fc{gamma}R-targeted antigens. When OVA was selectively targeted to hFc{gamma}RI, few differences were observed between Tg and NTg DC. However, upon co-incubation with CpG ODN, hFc{gamma}RI-triggered cross presentation was enhanced. These results document the capacity of hFc{gamma}RI on DC to trigger cross presentation via MHC class I upon co-culture with CpG ODN.

Keywords: antigen presentation, antigen targeting, bacterial DNA, MHC class I

Transmitting editor: S. Izui


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