Isoaspartyl post-translational modification triggers autoimmune responses to self-proteins.

摘要: The normal functioning immune system is programmed to attack foreign pathogens and other proteins while maintaining tolerance self-proteins. mechanisms by which broken in the initiation of autoimmunity are not completely understood. In present study, mice immunized with murine cytochrome c peptide 90–104 showed no response B or T cell compartments. However, immunization isoaspartyl form this peptide, where linkage Asp93 Leu94 occurs through β-carboxyl group, resulted strong autoimmune responses. Antibodies elicited self-peptide were cross-reactive binding both isoforms cpeptide native self-protein. a similar manner, autoantigen human systemic lupus erythematosus (SLE) responses maintained aspartyl self-antigen. Isoaspartyl linkages within enhanced aging stressed cells arise under physiological conditions. These post-translationally modified peptides may serve as an early immunologic stimulus disease.