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Cancer Immunol Immunother ; 65(5): 551-62, 2016 May.
Article in English | MEDLINE | ID: mdl-26969612

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.


Subject(s)
Antigens, CD1d/immunology , B-Lymphocytes/immunology , Cell Communication/immunology , G(M3) Ganglioside/immunology , Natural Killer T-Cells/immunology , Adult , Antigen Presentation/immunology , Antigens, CD1d/metabolism , B-Lymphocytes/metabolism , Cell Line , Cell Proliferation , Cells, Cultured , Coculture Techniques , Flow Cytometry , G(M3) Ganglioside/metabolism , Humans , Ligands , Lymphocyte Activation/immunology , Natural Killer T-Cells/metabolism , Palatine Tonsil/cytology , Protein Binding/immunology
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