Evidence for a role of ganglioside GM(1) 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-sur face receptors, targeting to compartments of antigen processing, surface ex pression 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 tra nsduction pathways. Using the a subunit of Escherichia coll enterotoxin (Et xB), a potent immunogen that binds GM1 with high affinity, and a non-bindin g mutant of EtxB, EtxB((G33D)), we demonstrate that GM(1) is intimately inv olved in several aspects of antigen presentation. Thus, GM(1)-mediated pres entation 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 b inding directly augments the expression of MHC class H on B cells, and frac tionation of a cells demonstrated that EtxB binding to GM(1) results in rap id internalization and targeting to class II-rich compartments. GM(1)-media ted uptake of antigens and access to class II compartments in B cells can b e exploited to significantly enhance the presentation of ovalbumin-conjugat ed to EtxB. These results demonstrate that GM(1) can play an important role in antigen presentation via the MHC II pathway.