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: Nicola P Jackson, Yu Hui Kang, Nicolas Lapaque, Hans Janssen, John Trowsdale, Adrian P Kelly
• Journal: European journal of immunology (Eur J Immunol) Vol. 43 Issue 4 Pg. 897-906 (Apr 2013) ISSN: 1521-4141 [Electronic] Germany
• PMID: 23319341 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Antigens, Bacterial
• Antigens, Differentiation, B-Lymphocyte
• Clathrin
• Histocompatibility Antigens Class II
• Peptides
• invariant chain

Topics

• Antigen Presentation (immunology)
• Antigens, Bacterial (chemistry, immunology)
• Antigens, Differentiation, B-Lymphocyte (metabolism)
• CD4-Positive T-Lymphocytes (immunology)
• Cell Line
• Cells, Cultured
• Clathrin (metabolism)
• Histocompatibility Antigens Class II (immunology, metabolism)
• Humans
• Multivesicular Bodies (metabolism)
• Peptides (immunology, metabolism)
• Protein Transport
• Salmonella (immunology)
• Salmonella Infections (immunology)