title: The tumor antigen N-glycolyl-GM3 is a human CD1d ligand capable of mediating B cell and natural killer T cell interaction.
abstract: The expression of N-glycolyl-monosialodihexosyl-ganglioside (NGcGM3) in humans is restricted to cancer cells; therefore, it is a tumor antigen. There are measurable quantities of circulating anti-NGcGM3 antibodies (aNGcGM3 Abs) in human serum. Interestingly, some people have circulating Ag-specific immunoglobulins G (IgGs) that are capable of complement mediated cytotoxicity against NGcGM3 positive cells, which is relevant for tumor surveillance. In light of the chemical nature of Ag, we postulated it as a candidate ligand for CD1d. Furthermore, we hypothesize that the immune mechanism involved in the generation of these Abs entails cross talk between B lymphocytes (Bc) and invariant natural killer T cells (iNKT). Combining cellular techniques, such as flow cytometry and biochemical assays, we demonstrated that CD1d binds to NGcGM3 and that human Bc present NGcGM3 in a CD1d context according to two alternative strategies. We also showed that paraformaldehyde treatment of cells expressing CD1d affects the presentation. Finally, by co-culturing primary human Bc with iNKT and measuring Ki-67 expression, we detected a reproducible increment in the proliferation of the iNKT population when Ag was on the medium. Our findings identify a novel, endogenous, human CD1d ligand, which is sufficiently competent to stimulate iNKT. We postulate that CD1d-restricted Bc presentation of NGcGM3 drives effective iNKT activation, an immunological mechanism that has not been previously described for humans, which may contribute to understanding aNGcGM3 occurrence.
authors.affiliation: Institute of Immunology, Genetics and Metabolism (INIGEM), Clinical Hospital, University of Buenos Aires, National Council for Scientific and Technological Research, Av Córdoba 2351, C1120AAF, Buenos Aires, Argentina.
authors.forename: M Virginia
authors.initials: MV
authors.lastname: Gentilini
authors.affiliation: Institute of Immunology, Genetics and Metabolism (INIGEM), Clinical Hospital, University of Buenos Aires, National Council for Scientific and Technological Research, Av Córdoba 2351, C1120AAF, Buenos Aires, Argentina.|Department of Immunogenetics, School of Exact Sciences, University of Misiones, Posadas, Misiones, Argentina.
authors.forename: M Eugenia
authors.initials: ME
authors.lastname: Pérez
authors.affiliation: Institute of Immunology, Genetics and Metabolism (INIGEM), Clinical Hospital, University of Buenos Aires, National Council for Scientific and Technological Research, Av Córdoba 2351, C1120AAF, Buenos Aires, Argentina.|Department of Immunology, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Pablo Mariano
authors.initials: PM
authors.lastname: Fernández
authors.affiliation: Institute of Immunology, Genetics and Metabolism (INIGEM), Clinical Hospital, University of Buenos Aires, National Council for Scientific and Technological Research, Av Córdoba 2351, C1120AAF, Buenos Aires, Argentina.|Department of Immunology, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Fainboim
authors.affiliation: Institute of Immunology, Genetics and Metabolism (INIGEM), Clinical Hospital, University of Buenos Aires, National Council for Scientific and Technological Research, Av Córdoba 2351, C1120AAF, Buenos Aires, Argentina. earana@hospitaldeclinicas.uba.ar.|Department of Immunology, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina. earana@hospitaldeclinicas.uba.ar.
authors.forename: Eloísa
authors.initials: E
authors.lastname: Arana
mesh_terms: D000328:Adult; D017951:Antigen Presentation / Q000276:immunology; D055610:Antigens, CD1d / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D005434:Flow Cytometry; D005679:G(M3) Ganglioside / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D014066:Palatine Tonsil / Q000166:cytology; D011485:Protein Binding / Q000276:immunology
chemical_list: D055610:Antigens, CD1d; C526877:CD1D protein, human; D005679:G(M3) Ganglioside; D008024:Ligands
keywords: B cells; CD1d; Gangliosides; Invariant natural killer T cells; Tumor antigen