The tumor antigen N-glycolyl-GM3 is a human CD1d ligand capable of mediating B cell and natural killer T cell interaction.

Autor: Gentilini MV; 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., Pérez ME; 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., Fernández PM; 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., Fainboim L; 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., Arana E; 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.
Jazyk: angličtina
Zdroj: Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2016 May; Vol. 65 (5), pp. 551-62. Date of Electronic Publication: 2016 Mar 11.
DOI: 10.1007/s00262-016-1812-y
Abstrakt: 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.
Databáze: MEDLINE