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 costimulatory signals. Ganglioside GM(1) is an important component of membrane glycosphingolipids, and has been implicated in cell differentiation, apoptosis and signal transduction pathways. Using the a subunit of Escherichia coll enterotoxin (EtxB), a potent immunogen that binds GM1 with high affinity, and a non-binding mutant of EtxB, EtxB((G33D)), we demonstrate that GM(1) is intimately involved in several aspects of antigen presentation. Thus, GM(1)-mediated presentation of EtxB by a 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 H on B cells, and fractionation of a cells demonstrated that EtxB binding to GM(1) results in rapid internalization and targeting to class II-rich compartments. GM(1)-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 GM(1) can play an important role in antigen presentation via the MHC II pathway.