Anti-Sm Autoantibodies in Systemic Lupus Target Highly Basic Surface Structures of Complexed Spliceosomal Autoantigens

作者: Micah T. McClain , Paul A. Ramsland , Kenneth M. Kaufman , Judith A. James

DOI: 10.4049/JIMMUNOL.168.4.2054

关键词: Epitope mappingRibonucleoproteinBiochemistrySpliceosomal complexBiologyAntigenAutoimmunityLupus erythematosusPeptide sequenceEpitopeMolecular biology

摘要: Autoantibodies directed against spliceosomal proteins are a common and specific feature of systemic lupus erythematosus. These autoantibodies target collection proteins, including Sm B, B', D1, D2, D3. We define the antigenic targets D2 D3 examine their role in autoimmunity. Our results nine major epitopes, five on four epitopes have significantly higher (more basic) isoelectric points than do nonantigenic regions. In fact, this association is sufficient power to make point an excellent predictor antigenicity. The crystallographic structure now partially described. anti-Sm located surface respective three-dimensional complexed thereby suggesting that these accessible native configuration. All but one conspicuously avoid regions involved intermolecular interactions within complex. One (RGRGRGMGR) has significant sequence homology with region D1 (containing carboxyl-terminal glycine-arginine repeat), anti-D3 Abs cross-react epitope D1. demonstrate autoimmunity surfaces cross-reactive as well structural associations various Ags, may be induction lupus.

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