Identification of the minimal glycopeptide core recognized by T cells in a model for rheumatoid arthritis.
Collagen induced arthritis (CIA) is a common mouse model for rheumatoid arthritis. Two sets of truncated peptides derived from type II collagen have been prepared and tested for binding to A(q), a MHC-II molecule associated with development of CIA. Binding to A(q) correlated well with predictions from a computer-based model. T-cell hybridomas, obtained in CIA, were also used to study the ability of A(q) bound peptides to trigger a T-cell response. The minimal peptide epitope required for binding, as well as for giving a T-cell response, was determined to be CII260-267. In collagen this epitope is often glycosylated at hydroxylysine 264 and glycosylation has been shown to be an immunodominant feature in CIA. Synthesis and evaluation of CII260-267 carrying a beta-D-galactosyl moiety at position 264 revealed that this glycopeptide stimulated representative members from a panel of carbohydrate-specific T-cell hybridomas obtained in CIA.
Holm
Lotta
L
Organic Chemistry, Department of Chemistry, Umeå University, SE-901 87 Umeå, Sweden.
Kjellén
Peter
P
Holmdahl
Rikard
R
Kihlberg
Jan
J
D000595:Amino Acid Sequence; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology; D001665:Binding Sites; D002460:Cell Line; D024043:Collagen Type II / Q000737:chemistry / Q000276:immunology; D000939:Epitopes; D006020:Glycopeptides / Q000737:chemistry* / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000737:chemistry; D006825:Hybridomas; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000737:chemistry* / Q000276:immunology
D024043:Collagen Type II; D000939:Epitopes; D006020:Glycopeptides; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments