caa a22 4500 469090715 CHVBK 20180323133016.0 cr unu---uuuuu 170328e19920601xx s 000 0 eng 10.1007/BF00464707 doi (NATIONALLICENCE)springer-10.1007/BF00464707 B-cell epitopes of autoantigenic DNA-binding proteins [Elektronische Daten] [Chih-Hao Chou, Minoru Satoh, Jingsong Wang, Westley Reeves] Conclusions: Autoantibodies to chromatin-associated proteins are frequently present in sera from patients with SLE, and related disorders. Autoantibodies to conformational epitopes may constitute the majority of the immune response to chromatin-associated antigens, suggesting that intact chromatin may be the immunogen in SLE as well as in certain forms of drug-induced lupus (eg. in procainamide-induced lupus). The preferential reactivity of autoantibodies to histones, PCNA, and Ku with antigenic determinants that are exposed on the surface of the native antigens is consistent with this interpretation. Strikingly, autoantibodies to these antigens frequently bind within or near active or functional sites, such as the DNA binding site of Ku [29], the site of PCNA critical for its role in enhancing DNA synthesis by polymerase delta [52], the posttranslational modification sites of the histones [68], and the catalytic site of poly(ADP-ribose) polymerase [69]. The explanation for the frequent observation that autoantibodies inhibit function is not yet known. It is possible that this phenomenon is related to the generation of autoantibodies by molecular mimicry, and that the functional sites of foreign antigens may crossreact with self antigens having similar functional sites [9]. Alternatively, the targeting of functional sites by autoantibodies may reflect merely a similar requirement for active sites and antibody-recognition sites to be exposed on surface. Features that make a site suitable for interacting with other proteins (eg. enzymes) or nucleic acids (eg DNA binding sites) may also make it more easily recognized by antibodies. The amino acids critical for autoantibody binding have not, in any of these cases, been shown to be critical to function. Further mapping and/ or mutagenesis studies will be necessary to determine the significance of the targeting of active or functional sites by autoantibodies. Kluwer Academic Publishers, 1992 autoantibody nationallicence chromatin nationallicence histones nationallicence Ku nationallicence PCNA nationallicence Chou Chih-Hao Division of Rheumatology and Immunology, The University of North Carolina at Chapel Hill, 932 FLOB, CB# 7280, 27599, Chapel Hill, NC, USA aut Satoh Minoru Division of Rheumatology and Immunology, The University of North Carolina at Chapel Hill, 932 FLOB, CB# 7280, 27599, Chapel Hill, NC, USA aut Wang Jingsong Division of Rheumatology and Immunology, The University of North Carolina at Chapel Hill, 932 FLOB, CB# 7280, 27599, Chapel Hill, NC, USA aut Reeves Westley Division of Rheumatology and Immunology, The University of North Carolina at Chapel Hill, 932 FLOB, CB# 7280, 27599, Chapel Hill, NC, USA aut Molecular Biology Reports Kluwer Academic Publishers 16/3(1992-06-01), 191-198 0301-4851 16:3<191 1992 16 11033 https://doi.org/10.1007/BF00464707 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00464707 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Chou Chih-Hao Division of Rheumatology and Immunology, The University of North Carolina at Chapel Hill, 932 FLOB, CB# 7280, 27599, Chapel Hill, NC, USA aut NATIONALLICENCE 700 1- Satoh Minoru Division of Rheumatology and Immunology, The University of North Carolina at Chapel Hill, 932 FLOB, CB# 7280, 27599, Chapel Hill, NC, USA aut NATIONALLICENCE 700 1- Wang Jingsong Division of Rheumatology and Immunology, The University of North Carolina at Chapel Hill, 932 FLOB, CB# 7280, 27599, Chapel Hill, NC, USA aut NATIONALLICENCE 700 1- Reeves Westley Division of Rheumatology and Immunology, The University of North Carolina at Chapel Hill, 932 FLOB, CB# 7280, 27599, Chapel Hill, NC, USA aut NATIONALLICENCE 773 0- Molecular Biology Reports Kluwer Academic Publishers 16/3(1992-06-01), 191-198 0301-4851 16:3<191 1992 16 11033 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer