Glycosylation of type II collagen is of major importance for T cell tolerance and pathology in collagen-induced arthritis.
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | European Journal of Immunology |
Volume | 32 |
Issue number | 12 |
Pages (from-to) | 3776-84 |
Number of pages | 8 |
ISSN | 0014-2980 |
DOIs | |
Publication status | Published - 2002 |
Bibliographical note
Keywords: Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Autoimmunity; Collagen Type II; Cross Reactions; Female; Glycosylation; Humans; Immune Tolerance; Male; Mice; Mice, Inbred C3H; Mice, Transgenic; T-Lymphocytes
ID: 5122665