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

Int J Cancer. 1989 May 15;43(5):828-36. doi: 10.1002/ijc.2910430515.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology
  • Animals
  • Cytotoxicity, Immunologic* / drug effects
  • Drug Resistance
  • Glycoside Hydrolases / antagonists & inhibitors
  • Histocompatibility Antigens Class I / immunology*
  • Mice
  • Mice, Inbred DBA
  • Neoplasms, Experimental / immunology*
  • Oligosaccharides / immunology*
  • Peptide Mapping
  • Swainsonine
  • T-Lymphocytes, Cytotoxic / immunology*
  • Trypsin
  • Wheat Germ Agglutinins / immunology*

Substances

  • Alkaloids
  • Histocompatibility Antigens Class I
  • Oligosaccharides
  • Wheat Germ Agglutinins
  • Glycoside Hydrolases
  • Trypsin
  • Swainsonine