Immunization of mice with human 60-kd Ro peptides results in epitope spreading if the peptides are highly homologous between human and mouse
✍ Scribed by R. Hal Scofield; Kenneth M. Kaufman; Usman Baber; Judith A. James; John B. Harley; Biji T. Kurien
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 200 KB
- Volume
- 42
- Category
- Article
- ISSN
- 0004-3591
No coin nor oath required. For personal study only.
✦ Synopsis
Immunization with peptide fragments of autoantigens may lead to an immune response at both the T and B cell level that is directed not only at the immunogen, but also at the autoantigen from which the peptide came. In addition, a complex multicomponent particle may become the target of this expanded immune response. The purpose of this study was to determine the ability of several different peptides from 60-kd Ro to induce expansion of the immune response to the Ro/La RNP particle.
Methods. We immunized BALB/c mice with 3 different oligopeptides from human 60-kd Ro (or, SSA).
Results. Animals immunized with peptides either identical to or differing by only 1 amino acid developed autoimmunity to the entire Ro RNP particle. Animals immunized with a human peptide highly divergent from the corresponding mouse sequence developed an immune response to the immunogen only and showed little evidence of epitope spreading. Furthermore, these mice did not have antibodies that bound the poorly conserved mouse homolog peptide, and the antibody response to this peptide did not include IgG1.
Conclusion.
These data indicate that B lymphocytes specific for the self-peptide that is homologous to the immunogen are a critical determinant for spreading of the immune response to other components of self.
Anti-Ro (or, SSA) is found in the sera of a substantial fraction of persons with several autoimmune diseases, including systemic lupus erythematosus and Sjo ¨gren's syndrome (1). In addition, anti-Ro is found in the sera of mothers who give birth to infants with neonatal lupus, usually manifested by complete congenital heart block or a lupus-like skin disease. However, most of these mothers have evidence of neither lupus nor Sjo ¨gren's syndrome and are completely well. Some will go on to develop one of these diseases with followup, but most remain healthy (2-5). In fact, anti-Ro is demonstrable in healthy individuals more than any other rheumatic autoantibody. The anti-Ro in healthy persons is identical to that found in patients with systemic lupus erythematosus (SLE) or Sjo ¨gren's syndrome (6).
Despite being found in some normal subjects, there is evidence that anti-Ro is directly pathogenic, especially for skin disease (7) and neonatal heart block (8-10). Also, there are several other clinical associations of anti-Ro (11,12) for which there is little or no evidence of pathogenicity. This includes the association of anti-Ro with anti-La (SSB) and anti-52-kd Ro. All sera with anti-Ro defined by immunodiffusion have high-titer antibodies binding 60-kd Ro. Meanwhile, some of these sera also have antibodies binding the 48-kd La protein (anti-La) and/or antibodies binding 52-kd Ro. The 60-kd Ro protein exists non-covalently associated with the hY RNA, and La is at times a stable component of this complex . The relationship of 52-kd Ro to the Roribonucleoprotein complex has not been definitely established (15-16).