Evidence for a role of ganglioside GM1 in antigen presentation: binding enhances presentation of Escherichia coli enterotoxin B subunit (EtxB) to CD4(+) T cells.
Successful antigen presentation by antigen-presenting cells is governed by a number of factors including the efficiency of antigen capture by cell-surface receptors, targeting to compartments of antigen processing, surface expression of MHC II-peptide complexes and presence of co-stimulatory signals. Ganglioside GM1 is an important component of membrane glycosphingolipids, and has been implicated in cell differentiation, apoptosis and signal transduction pathways. Using the B subunit of Escherichia coli enterotoxin (EtxB), a potent immunogen that binds GM1 with high affinity, and a non-binding mutant of EtxB, EtxB(G33D), we demonstrate that GM1 is intimately involved in several aspects of antigen presentation. Thus, GM1-mediated presentation of EtxB by B cells and CD11c(+) dendritic cells (DC) significantly enhanced the proliferation and cytokine expression of EtxB-specific CD4(+) T cells. Investigation regarding potential mechanisms revealed that EtxB binding directly augments the expression of MHC class II on B cells, and fractionation of B cells demonstrated that EtxB binding to GM1 results in rapid internalization and targeting to class II-rich compartments. GM1-mediated uptake of antigens and access to class II compartments in B cells can be exploited to significantly enhance the presentation of ovalbumin-conjugated to EtxB. These results demonstrate that GM1 can play an important role in antigen presentation via the MHC II pathway.
Nashar
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TO
Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK.
Betteridge
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Mitchell
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RN
D000818:Animals; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004768:Enterotoxins / Q000276:immunology*; D005677:G(M1) Ganglioside / Q000378:metabolism / Q000502:physiology*; D005802:Genes, MHC Class II / Q000276:immunology; D016167:Integrin alphaXbeta2; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology*
D001427:Bacterial Toxins; D004768:Enterotoxins; D016167:Integrin alphaXbeta2; D008222:Lymphokines; D011956:Receptors, Cell Surface; C043695:lymphocyte proliferation potentiating factors; D005677:G(M1) Ganglioside