Mycobacterial heat shock protein 65 enhances antigen cross-presentation in dendritic cells independent of Toll-like receptor 4 signaling.
Heat shock proteins (HSP) have been shown to enhance antigen processing and presentation through their association with antigenic peptides and delivery of these moieties into major histocompatibility complex class I pathways. In this study, mycobacterial Hsp65 is demonstrated to have the ability to help cross-present an exogenous protein by dendritic cells (DC) to CD8 T cells without the need for complex formation between Hsp65 and the protein. This ability of Hsp65 to enhance cross-presentation is independent of its weak stimulatory effect on DC, the latter seen only after prolonged incubation. When the effect of lipopolysaccharide contamination is abrogated, Hsp65 is unable to activate Toll-like receptor (TLR)4 in the presence of CD14 and MD2. This accounts for the inability of Hsp65 to drive maturation of DC and shows that Hsp65 is not a potent stimulator of DC. Thus, Hsp65 enhances the cross-presentation of a soluble, free antigen by DC, independent of TLR4 signaling and up-regulation of costimulatory molecules.
Department of Biochemistry, Faculty of Medicine, National University of Singapore, Singapore 117597. bchganyh@nus.edu.sg
Kang
K
Chen
Jinhua
J
Lu
Lei
L
Wang
Yunn-Hwen
YH
Gan
D017951:Antigen Presentation / Q000276:immunology*; D000941:Antigens / Q000276:immunology*; D000954:Antigens, Surface; D001426:Bacterial Proteins / Q000276:immunology* / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D018834:Chaperonin 60; D018833:Chaperonins / Q000276:immunology* / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D018950:Lipopolysaccharide Receptors; D051218:Lymphocyte Antigen 96; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D015398:Signal Transduction; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D000941:Antigens; D000954:Antigens, Surface; D001426:Bacterial Proteins; D018834:Chaperonin 60; C495377:LY96 protein, human; D018950:Lipopolysaccharide Receptors; D051218:Lymphocyte Antigen 96; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins