Immunogenicity of autologous IgG bearing the inflammation-associated marker 3-nitrotyrosine.
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.
Ohmori
Hitoshi
H
Department of Biotechnology, Faculty of Engineering, Okayama University, Tsushima-Naka, Okayama 700-8530, Japan. hit2224@cc.okayama-u.ac.jp
Oka
Michio
M
Nishikawa
Yumiko
Y
Shigemitsu
Hiroyuki
H
Takeuchi
Masahiro
M
Magari
Masaki
M
Kanayama
Naoki
N
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D004247:DNA / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000276:immunology* / Q000378:metabolism
D000906:Antibodies; D007074:Immunoglobulin G; C002744:3-nitrotyrosine; D014443:Tyrosine; D004247:DNA