期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 43, 期 4, 页码 897-906出版社
WILEY-BLACKWELL
DOI: 10.1002/eji.201242983
关键词
Autoimmunity; Bacterial Infections; CD4 T cells; Tolerance
类别
资金
- Royal Society of New Zealand Rutherford Foundation
- Wellcome Trust
- National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre
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.
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