Immunogenicity of autologous IgG bearing the inflammation-associated marker 3-nitrotyrosine

Hitoshi Ohmori, Michio Oka, Yumiko Nishikawa, Hiroyuki Shigemitsu, Masahiro Takeuchi, Masaki Magari, Naoki Kanayama

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

To explore the link between inflammation and autoimmunity, we analyzed the immunogenicity of 3-nitrotyrosine (NT)-bearing self-proteins, an inflammation-associated marker that is formed by nitration of protein tyrosine residues with peroxynitrite generated during inflammation. An interesting feature of NT is its structural similarity to a synthetic hapten, 4-hydroxy-3-nitrophenylacetyl (NP), with which some anti-DNA antibodies (Abs) have been reported to show cross-reactivity. We confirmed that some of anti-DNA monoclonal Abs (mAbs) obtained from MRL/lpr mice also bound NT as well as NP. Based on these findings, we examined whether NT-bearing autologous IgG (NT-IgG) as a model of NT-self proteins is immunogenic to induce a DNA-cross-reactive anti-NT Ab response in autologous normal mice. Anti-NT IgM and IgG Ab responses were elicited after the third immunization with NT-IgG, concomitant with an increase in anti-single stranded (ss)DNA titer. Interestingly, a part of anti-NT mAbs thus induced showed cross-reactivity with ssDNA, some of which used VH sequences that were highly homologous to those reported in anti-DNA Abs from NZB/WF1 mice. Splenic T cells primed with NT-IgG, but not with unmodified IgG, showed a proliferative response to the inducing antigen. Collectively, NT-IgG is immunogenic in autologous hosts, and can induce anti-NT Abs that are cross-reactive with ssDNA.

Original languageEnglish
Pages (from-to)47-54
Number of pages8
JournalImmunology Letters
Volume96
Issue number1
DOIs
Publication statusPublished - Jan 15 2005

Keywords

  • Anti-DNA antibody
  • Autoantibody
  • Immunological tolerance
  • Tyrosine-nitrated protein

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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