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Abstract Two related sublines of the DBA/2 lymphoma L5178Y, which were originally selected for their markedly different susceptibility to natural killer (NK) cell-mediated lysis, were found to differ in their giycoiipid patterns: namely. the NK-sensitive line (clone 27V) contained a high level of the neutral giycoiipid asialo GM2 (GalNAcβ1→ 4Galβ1→4Glcβ1→1ceramide), whereas in the NK-resistant variant (clone 27AV) this giycoiipid was not detectable. Flow microfluorometry and C-dependent cytotoxicity with antibodies specific for asialo GM2 indicated that the clone 27V cells, but not the clone 27AV line, expressed asialo GM2 on their cell surfaces. Because asialo GM2 display was associated with NK susceptibility in the 2 lymphoma cell variants, we addressed directly the hypothesis that the giycoiipid was the substrate for NK attack. The clone 27V line was recloned, and subclones were tested for their binding to iodinated monoclonal anti-asialo GM2. None of the 26 subclones of clone 27V tested were unreactive with anti-asialo GM2 as was the clone 27AV line. The most reactive subclones bound 6- to ten-fold more antibody than the low-binding subclones and were approximately 50-fold more sensitive to lysis by anti-asialo GM2 plus C. However, the chemical quantity of asialo GM2 in the most reactive subclones were only 2 to 4 times greater than that in the least reactive subclones. Thus, immunologic reactivity was related not only to the concentration of antigen but also to the organizational state of the antigen at the cell surface. Heterogeneity in asialo GM2 display was not, however, associated with differences in susceptibility to NK cell attack, for all of the asialo GM2-positive subclones were lysed to an equivalent extent. In addition, NK cell-mediated lysis could not be inhibited by anti-asialo GM2 sera. Thus, although display of asialo GM2 on L5178Y cells was associated with susceptibility to NK attack, there was no correlation between asialo GM2 level and NK sensitivity.
Young et al. (1981) studied this question.