title: Role of the galactosyl moiety of collagen glycopeptides for T-cell stimulation in a model for rheumatoid arthritis.
abstract: Two protected derivatives of beta-D-galactopyranosyl-5-hydroxy-L-lysine, in which HO-4 of galactose has been O-methylated or replaced by fluorine, have been prepared. The building blocks were incorporated at position 264 of the peptide fragment CII259-273 from type II collagen by solid-phase synthesis. The ability of these two glycopeptides, and two CII259-273 glycopeptides in which HO-4 of galactose was either unmodified or deoxygenated, to elicit responses from T-cell hybridomas obtained in a mouse model for rheumatoid arthritis was then determined. The hybridomas were all highly sensitive towards modifications at C-4 of the beta-D-galactosyl residue of CII259-273, highlighting the role of HO-4 as an important contact point for the T-cell receptor. Most likely, this glycopeptide hydroxyl group is involved in hydrogen bonding with the T-cell receptor.
authors.affiliation: Organic Chemistry, Department of Chemistry, Umeå University, SE-901 87 Umeå, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Holm
authors.forename: Syed M
authors.initials: SM
authors.lastname: Baquer
authors.forename: Lotta
authors.initials: L
authors.lastname: Holm
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
authors.forename: Jan
authors.initials: J
authors.lastname: Kihlberg
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D024043:Collagen Type II / Q000737:chemistry* / Q000276:immunology; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D005690:Galactose / Q000737:chemistry* / Q000276:immunology; D006020:Glycopeptides / Q000138:chemical synthesis* / Q000276:immunology; D006825:Hybridomas / Q000276:immunology; D006901:Hydroxylysine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D024043:Collagen Type II; D006020:Glycopeptides; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D006901:Hydroxylysine; C007817:galactosylhydroxylysine; D005690:Galactose