Drs. Huizinga, Toes, and Ioan-Facsinay have a patent application pending for the use of the peptide sequences in tolerization protocols.
Rheumatoid Arthritis Basic Science Studies
Identification of citrullinated vimentin peptides as T cell epitopes in HLA–DR4–positive patients with rheumatoid arthritis
Article first published online: 28 DEC 2009
Copyright © 2010 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 62, Issue 1, pages 117–125, January 2010
How to Cite
Feitsma, A. L., van der Voort, E. I. H., Franken, K. L. M. C., El Bannoudi, H., Elferink, B. G., Drijfhout, J. W., Huizinga, T. W. J., de Vries, R. R. P., Toes, R. E. M. and Ioan-Facsinay, A. (2010), Identification of citrullinated vimentin peptides as T cell epitopes in HLA–DR4–positive patients with rheumatoid arthritis. Arthritis & Rheumatism, 62: 117–125. doi: 10.1002/art.25059
- Issue published online: 28 DEC 2009
- Article first published online: 28 DEC 2009
- Manuscript Accepted: 25 SEP 2009
- Manuscript Received: 29 APR 2009
- European Commission Sixth Framework Programme Autocure and European Commission Seventh Framework Programme Masterswitch
- Dutch Organization for Scientific Research (VIDI). Grant Number: VENI grant 916.46.079
Antibodies directed against citrullinated proteins (ACPAs) are highly specific for rheumatoid arthritis (RA). The production of ACPAs is most likely dependent on the presence of T cells, since ACPAs undergo isotype switching and are associated with the shared epitope (SE)–containing HLA–DRB1 alleles. Vimentin is a likely candidate protein for T cell recognition, since >90% of patients positive for ACPAs that are reactive with (peptides derived from) citrullinated vimentin carry SE-containing HLA–DRB1 alleles. The aim of this study was to identify citrullinated vimentin peptides that are presented to HLA–DRB1*0401–restricted T cells.
HLA–DR4–transgenic mice were immunized with all possible citrulline-containing peptides derived from vimentin, and T cell reactivity was analyzed. Peptides recognized in a citrulline-specific manner by T cells were selected and analyzed for their ability to be processed from the entire vimentin protein. A first inventory of the selected epitopes recognized by T cells was performed using peripheral blood mononuclear cells (PBMCs) from ACPA+, HLA–DR4+ patients with RA.
A citrulline-specific response was observed for 2 of the peptides analyzed in DR4-transgenic mice. These peptides were found to be naturally processed from the vimentin protein, since citrullinated vimentin was recognized by peptide-specific T cells. T cell reactivity against these peptides was also observed in cultures of PBMCs from RA patients.
This study identifies, for the first time, 2 naturally processed peptides from vimentin that are recognized by HLA–DRB1*0401–restricted T cells in a citrulline-specific manner. These peptides can be recognized by T cells in ACPA+, HLA–DR4+ patients with RA, as shown in a first inventory.