HUMAN ANTINUCLEAR RIBONUCLEOPROTEIN ANTIGEN AUTOIMMUNE SERA CONTAIN ANOVEL SUBSET OF AUTOANTIBODIES THAT STABILIZES THE MOLECULAR INTERACTION OF U1RNP-C PROTEIN WITH THE SM CORE PROTEINS

Anti-Sm Abs recognize Sm core proteins B'/B, D, E, F, and G, shared by U1, U2, U4-6, and U5 small nuclear ribonucleoproteins (snRNPs), while anti-nuclear ribonucleoprotein Ag (nRNP) Abs recognize the U1RNP-spec ific 70K, A, and C proteins. However, although the autoimmune response to U1 snRNPs involves all components of the particle, not all are rec ognized equally. For example, all human anti-nRNP sera contain Abs aga inst native U1-C, in contrast to their absence in MRL/lpr mice. In thi s study, autoantibody recognition of native U1 snRNPs was investigated by dissociating the particle into four components (U1-70K, U1-A, U1-C , and the Sm core particle) using 1 M MgCl2 or ribonuclease treatment. As expected, human anti-Sm and MRL/lpr sera immunoprecipitated only t he Sm core proteins, and human anti-nRNP/Sm sera immunoprecipitated th e Sm core proteins plus U1-C under both conditions. However, although human anti-nRNP sera immunoprecipitated U1-C when U1 snRNPs were disso ciated before Ab binding, they unexpectedly immunoprecipitated the Sm core proteins when Abs were bound before dissociation. This apparent p aradox was explained by the stabilizing effects of anti-nRNP sera on i nteractions of U1-C with the Sm core particle. All human anti-nRNP ser a contained high levels of autoantibodies that prevent dissociation of U1-C from the U1 snRNP. These Abs were absent in MRL/lpr mice. Human autoimmune sera may prevent dissociation by recognizing the quaternary structure of the U1-C-Sm core protein complex or by altering its conf ormation. Stabilization of U1 snRNPs by autoantibodies could influence Ag processing and presentation, possibly with important effects on th e development of autoimmunity to U1 snRNPs.