Immunogenicity of an inflammation-associated product, tyrosine nitrated self-proteins.
To understand the mechanism leading to autoantibody production, it is of importance to reveal how self-components that are otherwise inactive as antigens acquire immunogenicity. One possible mechanism is the generation of structurally modified self-proteins in apoptotic or inflamed tissues. The post-translational modification of proteins might give rise to the generation of new epitopes to which T and B lymphocytes are not rendered tolerant. Among the protein modifications, this review is focussed on the generation and the immunogenicity of self-proteins carrying 3-nitrotyrosine (NT), an inflammation-associated marker. NT-proteins are generated in vivo by nitration with peroxynitrite, which is formed from nitric oxide and superoxide that are released from activated inflammatory cells. Interestingly, many anti-DNA Abs from autoimmune mice have been shown cross-reactive with NT. Analysis of the immunogenicity of NT-carrying self-proteins has revealed that they elicit both humoral and cellular immune responses in mice. Thus, NT-containing epitopes created on self-proteins may serve as a trigger to impair or bypass immunological tolerance.
Ohmori
Hitoshi
H
Department of Bioscience and Biotechnology, Okayama University, Tsushima-Naka 3-1-1, Okayama 700-8530, Japan. hit2224@cc.okayama-u.ac.jp
Kanayama
Naoki
N
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001324:Autoantigens / Q000276:immunology* / Q000378:metabolism*; D000939:Epitopes / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000276:immunology* / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D011506:Proteins; C002744:3-nitrotyrosine; D014443:Tyrosine