Glycosylation of type II collagen is of major importance for T cell tolerance and pathology in collagen-induced arthritis.
Type II collagen (CII) is a candidate cartilage-specific autoantigen, which can become post-translationally modified by hydroxylation and glycosylation. T cell recognition of CII is essential for the development of murine collagen-induced arthritis (CIA) and also occurs in rheumatoid arthritis (RA). The common denominator of murine CIA and human RA is the presentation of an immunodominant CII-derived glycosylated peptide on murine Aq and human DR4 molecules, respectively. To investigate the importance of T cell recognition of glycosylated CII in CIA development after immunization with heterologous CII, we treated neonatal mice with different heterologous CII-peptides (non-modified, hydroxylated and galactosylated). Treatment with the galactosylated peptide (galactose at position 264) was superior in protecting mice from CIA. Protection was accompanied by a reduced antibody response to CII and by an impaired T cell response to the glycopeptide. To investigate the importance of glycopeptide recognition in an autologous CIA model, we treated MMC-transgenic mice, which express the heterologous CII epitope with a glutamic acid in position 266 in cartilage, with CII-peptides. Again, a strong vaccination potential of the glycopeptide was seen. Hence CII-glycopeptides may be the optimal choice of vaccination target in RA, since humans share the same epitope as the MMC mouse.
Bäcklund
Johan
J
Section of Medical Inflammation Research, BMC, Lund University, Lund, Sweden.
Treschow
Alexandra
A
Bockermann
Robert
R
Holm
Björn
B
Holm
Lotta
L
Issazadeh-Navikas
Shohreh
S
Kihlberg
Jan
J
Holmdahl
Rikard
R
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000276:immunology; D015551:Autoimmunity; D024043:Collagen Type II / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D003429:Cross Reactions; D005260:Female; D006031:Glycosylation; D006801:Humans; D007108:Immune Tolerance; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology*
D024043:Collagen Type II