TLR ligands differentially affect uptake and presentation of cellular antigens.
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.
Weck
Markus Michael
MM
Department of Oncology, Hematology, Immunology, Rheumatology and Pulmology, Internal Medicine II, Institute of Medical Virology, University of Tübingen, Otfried-Müller-Strasse 10, 72076 Tübingen, Germany.
Grünebach
Frank
F
Werth
Daniela
D
Sinzger
Christian
C
Bringmann
Anita
A
Brossart
Peter
P
D017951:Antigen Presentation; D017209:Apoptosis / Q000276:immunology; D002460:Cell Line; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000628:therapy; D003713:Dendritic Cells / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005347:Fibroblasts / Q000276:immunology / Q000821:virology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D009000:Monocytes / Q000276:immunology; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D010750:Phosphoproteins / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology*; D014611:Vaccination; D014763:Viral Matrix Proteins / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D010750:Phosphoproteins; D051193:Toll-Like Receptors; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa