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 (galactoseat 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

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

Nyckelord

Mice

Male

Immune Tolerance

Human

Glycosylation

Female

Inbred C3H

Non-U.S. Gov't

T-Lymphocytes: immunology

Transgenic

Collagen Type II: genetics

Collagen Type II: chemistry

Autoimmunity

Rheumatoid: immunology

Support

Cross Reactions

Collagen Type II: immunology

Arthritis

Animal

Experimental: immunology

Experimental: metabolism

Experimental: pathology

Rheumatoid: etiology

Publikations- och innehållstyp

art (ämneskategori)

ref (ämneskategori)