title: Different class I antigen oligosaccharides on a murine tumor and a lectin-resistant variant are not responsible for the differential recognition of the tumors by CTL.
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.
authors.affiliation: Department of Biochemistry, University of Toronto, Ontario, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Degen
authors.forename: S
authors.initials: S
authors.lastname: Laferté
authors.forename: B E
authors.initials: BE
authors.lastname: Elliott
authors.forename: D B
authors.initials: DB
authors.lastname: Williams
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004351:Drug Resistance; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D009374:Neoplasms, Experimental / Q000276:immunology*; D009844:Oligosaccharides / Q000276:immunology*; D010449:Peptide Mapping; D017026:Swainsonine; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014357:Trypsin; D014909:Wheat Germ Agglutinins / Q000276:immunology*
chemical_list: D000470:Alkaloids; D015395:Histocompatibility Antigens Class I; D009844:Oligosaccharides; D014909:Wheat Germ Agglutinins; D006026:Glycoside Hydrolases; D014357:Trypsin; D017026:Swainsonine