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The route of bacterial uptake by macrophages influences the repertoire of epitopes presented to CD4 T cells

Lookup NU author(s): Dr Alexei von Delwig, Professor John Robinson


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We studied MHC class II (MHC-II)-restricted antigen processing of viable Streptococcus pyogenes by murine macrophages for presentation of two CD4 T cell epitopes of the surface M5 protein. We show that presentation of both epitopes was prevented if actin polymerization was inhibited by cytochalasin D, but not if clathrin-dependent receptor-mediated endocytosis was prevented, suggesting uptake of streptococci by phagocytosis or macropinocytosis was required for presentation of the surface M protein. However, treatment of macrophages with amiloride, which selectively blocks membrane ruffling and subsequent macropinocytosis, inhibited the response to one epitope (M5308-319), but had no effect on presentation of the other (M517-31). The effect of the inhibitors on uptake of streptococci was analyzed by electron microscopy. Cytochalasin D completely blocked uptake of streptococci, while dimethyl-amiloride only inhibited uptake into spacious compartments. Neither of the inhibitors altered the cell-surface expression of MHC-II and costimulatory molecules analyzed by flow cytometry. The data suggest that distinct epitopes of a protein associated with viable bacteria may be presented optimally following different uptake mechanisms in the same antigen -presenting cells.

Publication metadata

Author(s): von Delwig A, Bailey E, Gibbs DM, Robinson JH

Publication type: Article

Publication status: Published

Journal: European Journal of Immunology

Year: 2002

Volume: 32

Issue: 12

Pages: 3714-3719

ISSN (print): 0014-2980

ISSN (electronic): 1521-4141

Publisher: Wiley - VCH Verlag GmbH & Co. KGaA


DOI: 10.1002/1521-4141(200212)32:12<3714::AID-IMMU3714>3.0.CO;2-Y

PubMed id: 12516565


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