The major T cell epitope on type II collagen is glycosylated in normal cartilage but modified by arthritis in both rats and humans.
Type II collagen (CII) is a target for autoreactive T cells in both rheumatoid arthritis and the murine model collagen-induced arthritis. The determinant core of CII has been identified as CII260-270, and the alteration of this T cell epitope by posttranslational modifications is known to be critical for development of arthritis in mice. Using CII-specific T cell hybridomas we have now shown that the immunodominant T cell epitope in the normal (healthy) human and rat joint cartilage is O-glycosylated at the critical T cell receptor recognition position 264 with a mono- or di-saccharide attached to a hydroxylysine. In contrast, in the arthritic human and rat joint cartilage there are both glycosylated and non-glycosylated CII forms. Glycosylated CII from normal cartilage could not be recognized by T cells reactive to peptides having only lysine or hydroxylysine at position 264, showing that antigen-presenting cells could not degrade the O-linked carbohydrate. Thus, the variable forms of the glycosylated epitope are determined by the structures present in cartilage, and these vary during the disease course. We conclude that the chondrocyte determines the structures presented to the immune system and that these structures are different in normal versus arthritic states.
Dzhambazov
Balik
B
Department of Cell and Molecular Biology, Section for Medical Inflammation Research, Lund University, Lund, Sweden.
Holmdahl
Meirav
M
Yamada
Hisakata
H
Lu
Shemin
S
Vestberg
Mikael
M
Holm
Björn
B
Johnell
Olof
O
Kihlberg
Jan
J
Holmdahl
Rikard
R
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001168:Arthritis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D002356:Cartilage / Q000276:immunology*; D024043:Collagen Type II / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006031:Glycosylation; D006801:Humans; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology
D024043:Collagen Type II; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments