Carbohydrate antigens rarely provide target epitopes for cytotoxic T lymphocytes (CTL). Disialoganglioside GD2 is a glycolipid expressed at high levels in human tumors and a small group of murine lymphomas (EL4, RBL5, RMA, RMA-S, A13, and BALBRVE). Immunization of C57B1/6 mice with irradiated EL4 cells stimulated a specific CTL response and protected these animals from engraftment of EL4 lymphoma. The CTL activity resided in the CD4-CD8+ population, was dependent on T cell receptor alpha/beta, and was not removed by anti-natural killer cell immunoabsorption, but was restricted to GD2 and H-2b bearing targets. CTL activity could be completely inhibited by GD2-oligosaccharide-specific monoclonal antibodies and their F(ab')2 fragments, but not by immunoglobulin G3 myelomas or antibodies against GD3 or GM2. Soluble GD2 did not inhibit specific tumor lysis. RMA-S lymphoma cells (GD2+H-2b-TAP2 deficient) were resistant to GD2-specific CTL. Sialic acid-containing peptides eluted from EL4 lymphoma cells could (a) stabilize H-2 molecules on RMA-S cells and (b) sensitize them for GD2-specific CTL. Control peptides (derived from vesicular stomatitis virus nucleoprotein peptide and GD2-negative lymphomas) could also stabilize H-2 on RMA-S, but were resistant to GD2-specific CTL. These H-2-binding peptides could be purified by anti-GD2 affinity chromatography. We postulate a new class of naturally occurring epitopes for T cells where branched-chain oligosaccharides are linked to peptides with anchoring motifs for the major histocompatibility complex class I pocket. While analogous to the haptens trinitrophenyl and O-beta-linked acetyl-glucosamine, the potential implications of natural carbohydrates as antigenic epitopes for CTL in biology are considerable.
Article|
July 01 1995
GD2 oligosaccharide: target for cytotoxic T lymphocytes.
X J Zhao,
X J Zhao
Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York 10021, USA.
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N K Cheung
N K Cheung
Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York 10021, USA.
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X J Zhao
Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York 10021, USA.
N K Cheung
Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York 10021, USA.
Online Issn: 1540-9538
Print Issn: 0022-1007
J Exp Med (1995) 182 (1): 67–74.
Citation
X J Zhao, N K Cheung; GD2 oligosaccharide: target for cytotoxic T lymphocytes.. J Exp Med 1 July 1995; 182 (1): 67–74. doi: https://doi.org/10.1084/jem.182.1.67
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