Dual Specificity and the Formation of Stable Autoimmune Complexes

✍ Scribed by Creg J. Workman; William P. Pfund; Edward W. Voss

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 192 KB
• Volume: 10
• Category: Article
• ISSN: 0952-3499
• DOI: 10.1002/(sici)1099-1352(199709/10)10:5<225::aid-jmr372>3.0.co;2-1

✦ Synopsis

Since dual specificity at the antibody active-site level involves new principles relative to monospecific antigenantibody interactions and may be a general property of autoantibodies, it was important to further characterize such antibodies. Four lupus derived autoantibodies were studied to understand parameters and mechanisms involved in the participation of dual-specific antibody molecules in the formation of highly stable immune complexes. Because the dual-specific binding properties of selected lupus-related murine autoantibodies had been previously described using a solid-phase polystyrene-based ELISA, a conformational sensitive membrane based assay (CSI) was used on a comparative basis to further characterize NZB/NZW F 1 murine monoclonal anti-DNA autoantibodies BV 04-01 (anti-ssDNA), BV 16-19 (anti-ssDNA), BV 17-45 (anti-dsDNA), and BV 16-13 (anti-dsDNA). All four monoclonal autoantibodies exhibited anti-IgG binding in the solid-phase ELISA. However in the CSI assay, only anti-dsDNA monoclonal autoantibodies BV 17-45 and BV 16-13 demonstrated anti-IgG binding, while anti-ssDNA autoantibodies BV 04-01 and BV 16-19 did not. Upon subjection to time-dependent thermal denaturation, with and without thiol reduction at 100°C in the CSI, the self-binding activities of BV 17-45 and BV 16-13 were abrogated demonstrating that the recognized IgG autoepitope(s) possessed conformational or discontinuous three-dimensional properties. The immunological implications of dual specificity are discussed on a structure-function basis and its correlation with formation of pathogenic immune complexes.