title: The alphabeta T cell response to self-glycolipids shows a novel mechanism of CD1b loading and a requirement for complex oligosaccharides.
abstract: The structural basis for the T cell recognition of lipoglycans remains to be elucidated. We have described autoreactive T cells responsive to GM1 ganglioside presented by CD1b. We show that glycosphingolipids bind to CD1b on the cell surface at neutral pH and are recognized without internalization or processing. Furthermore, soluble GM-CD1b complexes stimulate specific T cells. Oligosaccharide groups containing five or more sugars are required to build a minimal epitope for TCR recognition. This suggests a mechanism for T cell recognition of glycosphingolipids in which much of the CD1b-bound ligand is exposed. Binding to CD1b is a highly reversible process and other ceramide-containing glycosphingolipids displace GM1. These nonantigenic compounds act as blockers and may prevent harmful autoreactivity in vivo.
authors.affiliation: Experimental Immunology, Department of Research, University Hospital, Basel, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Shamshiev
authors.forename: A
authors.initials: A
authors.lastname: Donda
authors.forename: T I
authors.initials: TI
authors.lastname: Prigozy
authors.forename: L
authors.initials: L
authors.lastname: Mori
authors.forename: V
authors.initials: V
authors.lastname: Chigorno
authors.forename: C A
authors.initials: CA
authors.lastname: Benedict
authors.forename: L
authors.initials: L
authors.lastname: Kappos
authors.forename: S
authors.initials: S
authors.lastname: Sonnino
authors.forename: M
authors.initials: M
authors.lastname: Kronenberg
authors.forename: G
authors.initials: G
authors.lastname: De Libero
mesh_terms: D017951:Antigen Presentation; D018949:Antigens, CD1 / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005677:G(M1) Ganglioside / Q000276:immunology*; D008024:Ligands; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018949:Antigens, CD1; D018984:Epitopes, T-Lymphocyte; D008024:Ligands; D005677:G(M1) Ganglioside