Tissue transglutaminase enhances collagen type II-induced arthritis and modifies the immunodominant T-cell epitope CII260-270
2009 (English)In: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 39, no 9, 2412-2423 p.Article in journal (Refereed) Published
The calcium-dependent enzyme tissue transglutaminase (tTG) is associated with diverse biological functions, such as induction of apoptosis, modeling of the extracellular matrix, receptor-mediated endocytosis, cell growth and differentiation, cell adhesion and signal transduction. Also, it may deamidate glutamine residues to glutamic acid and catalyze cross-linking of proteins. In this study, we have investigated the impact of tTG for posttranslational modifications and cross-linking of the immunodominant T-cell epitope CII260-270 and their effects on the collagen-induced arthritis, an animal model for rheumatoid arthritis. By using mass spectrometry analysis and hybridoma assays, we have demonstrated that tTG could perform both types of modifications (deamidation and cross-link formation) on the immunodominant T-cell epitope CII259-273. Replacement of the glutamine at position 267 with glutamic acid leads to a decreased binding affinity to MHC II. T cells recognized both non-modfied (Q(267)) and modified (E(267)) CII259-273-peptides. We also show that administration of tTG leads to increased incidence, severity and histopathological manifestations of collagen-induced arthritis in mice. Moreover, we conclude that both processes, deamidation and cross-linking, are involved in the tTG-catalyzed reactions, and in vivo administration of tTG enhances arthritis severity and joint destruction in mice.
Place, publisher, year, edition, pages
2009. Vol. 39, no 9, 2412-2423 p.
Collagen-induced arthritis, CII-peptide, Posttranslational modifications, T cells, Tissue transglutaminase
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-119527DOI: 10.1002/eji.200939438ISI: 000269786000015PubMedID: 19676074OAI: oai:DiVA.org:uu-119527DiVA: diva2:300382