Recognition of Salmonella by Dectin-1 induces presentation of peptide antigen to type B T cells.
Type B T cells recognize peptide-MHC class II (pMHCII) isoforms that are structurally distinct from those recognized by conventional type A T cells. These alternative type B conformers result from peptide loading in the absence of HLA-DM. Type A conformers are more stable than type B pMHCII conformers but bind the same peptide in the same register. Here, we show that interaction of Salmonella Typhimurium with bone marrow derived dendritic cells (BMDCs) isolated from C3H/HeNCr1 mice results in enhanced presentation of peptide Ag to type B T cells. The effect could be mimicked by purified PAMPs, the most potent of which were curdlan and zymosan, β-(1,3)-glucan-containing polymers that are recognized by Dectin-1. Blocking of Dectin-1 with Ab and laminarin inhibited the induction of the type B T-cell response by BMDCs, confirming its role as a PRR for S. Typhimurium. Splenic DCs (sDCs) expressed Dectin-1 but were refractive to the induction of type B responses by S. Typhimurium and curdlan. Type B T cells have been shown to escape thymic tolerance and to transfer pathology in an autoimmune disease model. The induction of type B responses by gram-negative bacteria provides a mechanism by which autoreactive T cells may be produced during infection.
Division of Immunology, Department of Pathology, University of Cambridge, Cambridge, UK.
Nicola
N
Jackson
Evan
E
Compton
John
J
Trowsdale
Adrian P
AP
Kelly
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D010455:Peptides / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology* / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000382:microbiology; D047071:beta-Glucans / Q000276:immunology; D000099181:Dectin-1
D000942:Antigens, Bacterial; D018122:B7-1 Antigen; D000949:Histocompatibility Antigens Class II; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D010455:Peptides; D047071:beta-Glucans; D000099181:Dectin-1; C038459:curdlan
Antigen presentation; Autoimmunity; Bacterial infection