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.