Scofield R H, Pierce P G, James J A, Kaufman K M, Kurien B T
Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Department of Medicine, University of Oklahoma Health Sciences Center and the Department of Veterans Affairs Medical Center, Oklahoma City, OK 73105, USA.
Scand J Immunol. 2002 Nov;56(5):477-83. doi: 10.1046/j.1365-3083.2002.01159.x.
Antibodies binding the Ro (or SSA) and La (or SBB) proteins are commonly found in a high proportion of sera from patients with systemic lupus erythematosus or Sjögren's syndrome. The mechanism by which these autoantibodies arise is not known. Others and we have shown that immunization of nonautoimmune-prone mice with short peptides from the Ro ribonucleoprotein particle can induce autoimmunity to 60 kDa Ro and 52 kDa Ro as well as to the 48 kDa La protein after epitope spreading. We have explored the differences in the epitope spreading after 60 kDa Ro peptide immunization in several strains of mice. There is intra- and intermolecular diversification of the immune response after immunization of DBA/2J animals with a monomer peptide representing the residues 480-494 of the 60 kDa Ro protein, but this peptide does not induce epitope spreading when used as the immunogen in either C57Bl/6J or PL/J mice. Similar to previously studied BALB/c mice, DBA/2J mice have antibodies binding many epitopes of 60 kDa Ro, and some sera bind 52 kDa Ro as well as La. These mice have antinuclear antibody in their sera. These data demonstrate that Ro peptide immunization results in different outcomes depending upon the strain of mouse used. Furthermore, these data suggest that genetic variation is important with regard to responding towards short peptide immunization by epitope spreading.
结合Ro(或SSA)和La(或SSB)蛋白的抗体常见于系统性红斑狼疮或干燥综合征患者的血清中,比例较高。这些自身抗体产生的机制尚不清楚。我们和其他人已经表明,用来自Ro核糖核蛋白颗粒的短肽免疫非自身免疫倾向的小鼠,在表位扩展后可诱导对60 kDa Ro和52 kDa Ro以及48 kDa La蛋白的自身免疫。我们已经探究了用60 kDa Ro肽免疫几种品系小鼠后表位扩展的差异。用代表60 kDa Ro蛋白480 - 494位残基的单体肽免疫DBA/2J动物后,免疫反应存在分子内和分子间的多样化,但当该肽用作C57Bl/6J或PL/J小鼠的免疫原时,不会诱导表位扩展。与先前研究的BALB/c小鼠相似,DBA/2J小鼠具有结合6许多0 kDa Ro表位的抗体,一些血清还结合52 kDa Ro以及La。这些小鼠血清中有抗核抗体。这些数据表明,Ro肽免疫的结果取决于所用小鼠的品系。此外,这些数据表明,在通过表位扩展对短肽免疫作出反应方面,基因变异很重要。