title: Salmonella polarises peptide-MHC-II presentation towards an unconventional Type B CD4+ T-cell response.
abstract: Distinct peptide-MHC-II complexes, recognised by Type A and B CD4(+) T-cell subsets, are generated when antigen is loaded in different intracellular compartments. Conventional Type A T cells recognize their peptide epitope regardless of the route of processing, whereas unconventional Type B T cells only recognise exogenously supplied peptide. Type B T cells are implicated in autoimmune conditions and may break tolerance by escaping negative selection. Here we show that Salmonella differentially influences presentation of antigen to Type A and B T cells. Infection of bone marrow-derived dendritic cells (BMDCs) with Salmonella enterica serovar Typhimurium (S. Typhimurium) reduced presentation of antigen to Type A T cells but enhanced presentation of exogenous peptide to Type B T cells. Exposure to S. Typhimurium was sufficient to enhance Type B T-cell activation. Salmonella Typhimurium infection reduced surface expression of MHC-II, by an invariant chain-independent trafficking mechanism, resulting in accumulation of MHC-II in multi-vesicular bodies. Reduced MHC-II surface expression in S. Typhimurium-infected BMDCs correlated with reduced antigen presentation to Type A T cells. Salmonella infection is implicated in reactive arthritis. Therefore, polarisation of antigen presentation towards a Type B response by Salmonella may be a predisposing factor in autoimmune conditions such as reactive arthritis.
authors: Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors: Nicola P
authors: NP
authors: Jackson
authors: Yu Hui
authors: YH
authors: Kang
authors: Nicolas
authors: N
authors: Lapaque
authors: Hans
authors: H
authors: Janssen
authors: John
authors: J
authors: Trowsdale
authors: Adrian P
authors: AP
authors: Kelly
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D002966:Clathrin / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D057146:Multivesicular Bodies / Q000378:metabolism; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D021381:Protein Transport; D012475:Salmonella / Q000276:immunology*; D012480:Salmonella Infections / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D000944:Antigens, Differentiation, B-Lymphocyte; D002966:Clathrin; D000949:Histocompatibility Antigens Class II; D010455:Peptides; C045084:invariant chain