Correlation of glycosphingolipids and sialic acid in YAC-1 lymphoma variants with their sensitivity to natural killer-cell-mediated lysis

Abstract

Sialoglycoconjugates and glycosphingolipids were quantitated in a series of variants derived from the YAC-1 lymphoma, known to be highly sensitive to natural killer (NK)-cell-mediated lysis. The variants, which had widely diverging sensitivities to NK cells, were obtained by a number of methods, including selection in the presence of NK cells, antibody to H-2, or antibody to the murine leukemia-virus-induced antigen, and by fusion of sensitive cells with an NK-resistant cell line, A9HT. The sensitivities of these cells to NK-cell-mediated lysis did not correlate with their sensitivities to anti-H-2a cytotoxic T cells. While no correlation could be made between the NK-sensitivity of these variants and their total cellular sialic acid, a statistically significant inverse correlation was observed between the levels of percentage neuraminidase releasable surface sialic acid of total labelled sialyl components and sensitivity to NK cells. This correlation with cell surface sialic acid was observed with either endogenous or lymphocytic choriomeningitis virus-induced activated NK cells as effectors. Neuraminidase treatment of insensitive target cells caused a moderate increase in sensitivity but failed to render the resistant targets as sensitive as YAC-1. Analysis of glycosphingolipids among the variants revealed a strong positive correlation between the total cell neutral glycolipid with chromatographic migration of asialo-GM2 and sensitivity to endogenous or activated NK-cell-mediated lysis. Significant correlations were not found with any other neutral glycolipids. However, ganglioside homologues with chromatographic mobility of GM1, GD1a, GD1b, And GT also showed a positive correlation with both endogenous and activated NK-cell-mediated lysis. The ratio of asialo-GM2 to GM2 had a highly significant positive correlation with sensitivity. These correlative results suggest that asialo-GM2 and certain gangliosides could be involved in binding or lytic events in NK cell:target cell interactions, and that high levels of sialic acid and sialylation on the surface may inhibit and/or modify such interactions. Further studies with these YAC variants should be useful for examining the biochemical bases of target cell-effector cell interactions in the NK-system.