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

GENTILINI MV; PÉREZ ME.; FAINBOIM L; FERNANDEZ, PM; ARANA E

CANCER IMMUNOLOGY IMMUNOTHERAPY

SPRINGER

Lugar: Berlin; Año: 2016

0340-7004

The expression of N-Glycolyl-monosialodihexosyl-ganglioside (NGcGM3) in humans is restricted tocancer 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 circulatingAg specific immunoglobulins G (IgGs) that are capable of complement mediated cytotoxicity againstNGcGM3 positive cells, which is relevant for tumor surveillance. In light of the chemical nature ofAg, we postulated it is a candidate ligand for CD1d. Furthermore, we hypothesize that the immunemechanism involved in the generation of these Abs involves cross talk between B lymphocytes (Bc)and invariant NKT cells (iNKT).Combining cellular techniques, such as flow cytometry and biochemical assays, we demonstratedthat CD1d binds to NGcGM3 and that human Bc present NGcGM3 in a CD1d context according totwo alternative strategies. We also showed that paraformaldehyde (PFA) treatment of cellsexpressing CD1d affects the presentation. Finally, by co-culturing primary human Bc with iNKT andmeasuring Ki-67 expression, we detected a reproducible increment in the proliferation of the iNKTpopulation when Ag was on the medium.Our findings identify a novel, endogenous, human CD1d ligand, which is sufficiently competent tostimulate iNKT. We postulate that CD1d-restricted Bc presentation of NGcGM3 drives effectiveiNKT activation, an immunological mechanism that has not been previously described for humans,which may contribute to understanding aNGcGM3 occurrence.