Bone and Joint Institute
The influence of MHC class II molecules containing the rheumatoid arthritis shared epitope on the immune response to aggrecan G1 and its peptides
Document Type
Article
Publication Date
5-1-2007
Journal
Scandinavian Journal of Immunology
Volume
65
Issue
5
First Page
444
Last Page
452
URL with Digital Object Identifier
10.1111/j.1365-3083.2007.01931.x
Abstract
Aggrecan has been implied as an autoantigen in rheumatoid arthritis (RA). Immunization with aggrecan induces arthritis in BALB/c (H-2d) mice but not in other strains of mice [e.g. C57BL/6 (H-2b)]. In humans, the strongest genetic association with RA is to the shared epitope (SE), and aggrecan peptides are predicted to bind to the SE. Therefore, we hypothesized that C57BL/6 mice transgenic (tg) for the RA SE (DR4 tg mice) may be susceptible to aggrecan-induced arthritis. C57BL/6 and DR4 tg mice were immunized with a mixture of SE-binding aggrecan peptides and tested for immune responses to the corresponding peptides as well as aggrecan. Sustained T- and B-cell immune responses to aggrecan and several of its peptides were detected in DR4 tg mice. C57BL/6 mice showed only transient T-cell responses to different immunizing peptides and little B-cell response. Therefore, an immune response to peptides of aggrecan can be induced experimentally in DR4 tg mice as anticipated from the predicted and actual binding affinities of these peptides for the RA SE. Failure to induce arthritis in these DR4 tg mice may be due to a lack of appropriate non-MHC genes. © 2007 The Authors.
Notes
Article is freely available from the journal