Human anti-nuclear ribonucleoprotein antigen autoimmune sera contain a novel 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 U1 RNP-specific 70K, A, and C proteins. However, although the autoimmune response to U1 snRNPs involves all components of the particle, not all are recognized equally. For example, all human anti-nRNP sera contain Abs against native U1-C, in contrast to their absence in MRL/lpr mice. In this 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 the Sm core proteins, and human anti-nRNP/Sm sera immunoprecipitated the Sm core proteins plus U1-C under both conditions. However, although human anti-nRNP sera immunoprecipitated U1-C when U1 snRNPs were dissociated before Ab binding, they unexpectedly immunoprecipitated the Sm core proteins when Abs were bound before dissociation. This apparent paradox was explained by the stabilizing effects of anti-nRNP sera on interactions of U1-C with the Sm core particle. All human anti-nRNP sera 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 conformation. Stabilization of U1 snRNPs by autoantibodies could influence Ag processing and presentation, possibly with important effects on the development of autoimmunity to U1 snRNPs.
Satoh
M
M
Department of Medicine, University of North Carolina, Chapel Hill 27599, USA.
Richards
H B
HB
Hamilton
K J
KJ
Reeves
W H
WH
D000818:Animals; D000937:Antigen-Antibody Reactions; D001323:Autoantibodies / Q000737:chemistry*; D001324:Autoantigens / Q000737:chemistry* / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D019463:Mice, Inbred MRL lpr; D011233:Precipitin Tests; D011485:Protein Binding; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000737:chemistry* / Q000276:immunology; D017411:Ribonucleoproteins, Small Nuclear / Q000737:chemistry* / Q000276:immunology; D055517:snRNP Core Proteins
D001323:Autoantibodies; D001324:Autoantigens; D046911:Macromolecular Substances; D017412:Ribonucleoprotein, U1 Small Nuclear; D017411:Ribonucleoproteins, Small Nuclear; C491260:SNRPC protein, human; C104347:Snrp1c protein, mouse; D055517:snRNP Core Proteins