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Carbamylation-Dependent Activation of T Cells: A Novel Mechanism in the Pathogenesis of Autoimmune Arthritis

Mydel, Piotr; Wang, Zhenning LU ; Brisslert, Mikael; Hellvard, Annelie; Dahlberg, Leif LU ; Hazen, Stanley L. and Bokarewa, Maria (2010) In Journal of Immunology 184(12). p.6882-6890
Abstract
The posttranslational modification of proteins has the potential to generate neoepitopes that may subsequently trigger immune responses. The carbamylation of lysine residues to form homocitrulline may be a key mechanism triggering inflammatory responses. We evaluated the role of carbamylation in triggering immune responses and report a new role for this process in the induction of arthritis. Immunization of mice with homocitrulline-containing peptides induced chemotaxis, T cell activation, and Ab production. The mice also developed erosive arthritis following intra-articular injection of peptides derived from homocitrulline and citrulline. Adoptive transfer of T and B cells from homocitrulline-immunized mice into normal recipients induced... (More)
The posttranslational modification of proteins has the potential to generate neoepitopes that may subsequently trigger immune responses. The carbamylation of lysine residues to form homocitrulline may be a key mechanism triggering inflammatory responses. We evaluated the role of carbamylation in triggering immune responses and report a new role for this process in the induction of arthritis. Immunization of mice with homocitrulline-containing peptides induced chemotaxis, T cell activation, and Ab production. The mice also developed erosive arthritis following intra-articular injection of peptides derived from homocitrulline and citrulline. Adoptive transfer of T and B cells from homocitrulline-immunized mice into normal recipients induced arthritis, whereas systemic injection of homocitrulline-specific Abs or intra-articular injection of homocitrulline-Ab/citrulline-peptide mixture did not. Thus, the T cell response to homocitrulline-derived peptides, as well as the subsequent production of anti-homocitrulline Abs, is critical for the induction of autoimmune reactions against citrulline-derived peptides and provides a novel mechanism for the pathogenesis of arthritis. The Journal of Immunology, 2010, 184: 6882-6890. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Immunology
volume
184
issue
12
pages
6882 - 6890
publisher
American Association of Immunologists
external identifiers
  • wos:000278516700036
  • scopus:77953627756
ISSN
1550-6606
DOI
10.4049/jimmunol.1000075
language
English
LU publication?
yes
id
54fdfb3b-9f2d-4b2c-871c-975554bd9459 (old id 1630972)
date added to LUP
2010-07-22 13:29:56
date last changed
2018-06-17 04:10:44
@article{54fdfb3b-9f2d-4b2c-871c-975554bd9459,
  abstract     = {The posttranslational modification of proteins has the potential to generate neoepitopes that may subsequently trigger immune responses. The carbamylation of lysine residues to form homocitrulline may be a key mechanism triggering inflammatory responses. We evaluated the role of carbamylation in triggering immune responses and report a new role for this process in the induction of arthritis. Immunization of mice with homocitrulline-containing peptides induced chemotaxis, T cell activation, and Ab production. The mice also developed erosive arthritis following intra-articular injection of peptides derived from homocitrulline and citrulline. Adoptive transfer of T and B cells from homocitrulline-immunized mice into normal recipients induced arthritis, whereas systemic injection of homocitrulline-specific Abs or intra-articular injection of homocitrulline-Ab/citrulline-peptide mixture did not. Thus, the T cell response to homocitrulline-derived peptides, as well as the subsequent production of anti-homocitrulline Abs, is critical for the induction of autoimmune reactions against citrulline-derived peptides and provides a novel mechanism for the pathogenesis of arthritis. The Journal of Immunology, 2010, 184: 6882-6890.},
  author       = {Mydel, Piotr and Wang, Zhenning and Brisslert, Mikael and Hellvard, Annelie and Dahlberg, Leif and Hazen, Stanley L. and Bokarewa, Maria},
  issn         = {1550-6606},
  language     = {eng},
  number       = {12},
  pages        = {6882--6890},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {Carbamylation-Dependent Activation of T Cells: A Novel Mechanism in the Pathogenesis of Autoimmune Arthritis},
  url          = {http://dx.doi.org/10.4049/jimmunol.1000075},
  volume       = {184},
  year         = {2010},
}