| Abstract: |
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, RBLS, 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 αβ, 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-β-linked acetyl-glucosamine, the potential implications of natural carbohydrates as antigenic epitopes for CTL in biology are considerable. © 1995, Rockefeller University Press., All rights reserved. |
| Keywords: |
controlled study; nonhuman; cd8 antigen; animal cell; mouse; animal; mice; gene targeting; animal model; neurons; pathology; tumor cells, cultured; tumor antigen; mice, inbred balb c; mice, inbred c57bl; t lymphocyte receptor; immunology; antigens, neoplasm; cell culture; nude mouse; mice, nude; epitope; cytotoxic t lymphocyte; t-lymphocytes, cytotoxic; rat; lymphoma; ligand; natural killer cell; rats; cd4 antigen; neoplasm transplantation; immunoglobulin g3; mouse strain; major histocompatibility complex; nerve cell; lymphocyte antigen receptor; ganglioside gm2; carbohydrate antigen; receptors, antigen, t-cell, alpha-beta; major histocompatibility antigen class 1; cancer transplantation; immunization; oligosaccharide; epitopes; gangliosides; ganglioside; affinity chromatography; ganglioside, gd2; mice, inbred dba; sialic acid; h-2 antigens; priority journal; article; h2 antigen; mast cell leukemia; support, non-u.s. gov't; glucosamine derivative; leukemia, basophilic, acute; receptors, antigen, t cell, alpha beta; trinitrophenyl; h 2 antigens
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