Abstract
Previous studies have shown that whereas a highly malignant mouse cell line termed MDAY-D2 (d haplotype) does not elicit a detectable response by cytotoxic T lymphocytes (CTL) in DBA/2 mice, strong anti-tumor CTL are generated against a wheat-germ-agglutinin-resistant variant, designated MDW3. Additional evidence suggests these anti-MDW3 CTL may not be a consequence of a unique antigenic determinant on the variant cells. Because MDW3 cells are expected to differ from MDAY-D2 cells in their surface carbohydrate structures (due to their lectin resistance) and Class I major histocompatibility molecules play a crucial role in CTL-mediated responses, we speculated that the Asn-linked oligosaccharides present on Class I molecules of MDAY-D2 and MDW3 might be different and could potentially influence recognition analyses and Con A-Sepharose affinity chromatography clearly demonstrated that the oligosaccharides isolated from the H-2Dd molecule of MDAY-D2 cells are larger and more highly branched than those of the MDW3 variant. Taken together with the finding that anti-MDW3 CTL are restricted by H-2Dd, these results suggested that the larger H-2Dd oligosaccharides on MDAY-D2 cells could potentially mask or perturb determinants required for recognition by these CTL. To test this postulate, the surface Class I oligosaccharides of both MDAY-D2 and MDW3 cells were converted to simpler hybrid structures by treatment with the oligosaccharide processing inhibitor, swainsonine. However, no effect was observed on the lysis or binding of either MDAY-D2 or MDW3 cells by anti-MDW3 CTL. Thus, the results do not support the possibility that the larger H-2Dd oligosaccharides on MDAY-D2 cells are, in themselves, responsible for the poor recognition of the parent tumor by anti-MDW3 CTL. Our data do indicate, however, that CTL target binding and effector functions are not dependent on the fine structure of complex Asn-linked carbohydrates present on Class I molecules and possibly on other, accessory molecules at the target cell surface, since MDW3 cells maintained their sensitivity to lysis by CTL following swainsonine treatment.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have