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Blood, 1 May 2007, Vol. 109, No. 9, pp. 3890-3894.
Prepublished online as a Blood First Edition Paper on January 11, 2007; DOI 10.1182/blood-2006-04-015719.


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IMMUNOBIOLOGY

TLR ligands differentially affect uptake and presentation of cellular antigens

Markus Michael Weck1, Frank Grünebach1, Daniela Werth1, Christian Sinzger2, Anita Bringmann1, and Peter Brossart1

1 Department of Oncology, Hematology, Immunology, Rheumatology and Pulmology and the 2 Institute of Medical Virology, University of Tübingen, Tübingen, Germany

Dendritic cells (DCs) have the unique ability to efficiently present T-cell epitopes from exogenous antigens on MHC class I molecules, a process called cross-presentation. In our study we demonstrate that stimulation of monocyte-derived DCs with Toll-like receptor (TLR) ligands differentially affects the uptake and cross-presentation of cellular antigens. Activation of DCs with TLR3 or TLR4 but not with TLR2 or TLR7/8 ligands inhibited phagocytosis of apoptotic tumor cells and resulted in a reduced cross-presentation of pp65-derived T-cell epitopes on MHC class I molecules upon engulfment of cytomegalovirus (CMV)–infected fibroblasts. These results have an important impact on the understanding of the interactions between the immune system and pathogens and the development of vaccination strategies to treat malignant diseases.


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