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Immune responses to Ro60 and its peptides in mice. I. The nature of the immunogen and endogenous autoantigen determine the specificities of the induced autoantibodies.

Deshmukh US, Lewis JE, Gaskin F, Kannapell CC, Waters ST, Lou YH, Tung KS, Fu SM - J. Exp. Med. (1999)

Bottom Line: With human Ro60316-335 as the immunogen, additional autoantibodies reactive with the Golgi complex were found.These results show that both the nature of the immunogen and the immunogenicity of the related endogenous antigen are important in determining the specificities of the autoantibodies generated.They have significant implications for proposed mechanisms on the generation of complex patterns of autoantibodies to a diverse group of autoantigens in SLE patients.

View Article: PubMed Central - PubMed

Affiliation: Division of Rheumatology, Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.

ABSTRACT
Anti-Ro60 autoantibodies are found in a variety of autoimmune disorders including systemic lupus erythematosus (SLE), Sjögren's syndrome, primary biliary cirrhosis, and active hepatitis. They are the most prevalent autoantibodies in normal individuals and in asymptomatic mothers of infants afflicted with neonatal lupus. In the present study, immune responses to recombinant human Ro60 (rhRo60) and recombinant mouse Ro60 (rmRo60) and selected Ro60 peptides in non-SLE-prone mice were investigated. Multiple T and B cell epitopes were identified in Ro60. Immunizations with either xenogeneic or autologous Ro60 induced autoantibodies to a diverse group of autoantigens. In addition to La and Ro52, proteins in the small nuclear ribonucleoprotein (snRNP) particles such as SmA, SmB, SmD, and 70-kD U1-RNP were unexpectedly identified as targeted antigens. In the studies involving synthetic Ro60 peptides, both human and mouse Ro60316-335 peptides, which differ in three amino acids, were found to contain dominant cross-reactive T cell determinants. Immunizations with these peptides induced autoantibodies to Ro60, La, SmD, and 70-kD U1-RNP without autoantibodies to Ro52, SmA, or SmB. With human Ro60316-335 as the immunogen, additional autoantibodies reactive with the Golgi complex were found. In contrast to the immunodominance of both human and mouse Ro60316-335 peptides, the T cell determinant in human Ro60441-465 was dominant, whereas that in the mouse peptide was cryptic. Immunization with human Ro60441-465 induced primarily anti-peptide Abs. Mouse Ro60441-465 failed to induce an antibody response. These results show that both the nature of the immunogen and the immunogenicity of the related endogenous antigen are important in determining the specificities of the autoantibodies generated. They have significant implications for proposed mechanisms on the generation of complex patterns of autoantibodies to a diverse group of autoantigens in SLE patients.

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Induction of ANAs  following immunization with  Ro60 antigens. Sera obtained on  day 67, postimmunization, were  pooled and used at a dilution of  1:200 to stain methanol-fixed  HeLa cells (detected by indirect  immunofluorescence). a, b, and c  represent sera from mice immunized with rmRo60, rhRo60,  and CFA, respectively.
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Figure 6: Induction of ANAs following immunization with Ro60 antigens. Sera obtained on day 67, postimmunization, were pooled and used at a dilution of 1:200 to stain methanol-fixed HeLa cells (detected by indirect immunofluorescence). a, b, and c represent sera from mice immunized with rmRo60, rhRo60, and CFA, respectively.

Mentions: Sera from SJL mice immunized with rmRo60 and rhRo60 were positive for antinuclear antibodies (ANA) (Fig. 6, A and B, respectively). Although results are shown for pooled sera, all mice had ANA in their sera. Such antibodies were not detected in mice immunized with only CFA (Fig. 6 C).


Immune responses to Ro60 and its peptides in mice. I. The nature of the immunogen and endogenous autoantigen determine the specificities of the induced autoantibodies.

Deshmukh US, Lewis JE, Gaskin F, Kannapell CC, Waters ST, Lou YH, Tung KS, Fu SM - J. Exp. Med. (1999)

Induction of ANAs  following immunization with  Ro60 antigens. Sera obtained on  day 67, postimmunization, were  pooled and used at a dilution of  1:200 to stain methanol-fixed  HeLa cells (detected by indirect  immunofluorescence). a, b, and c  represent sera from mice immunized with rmRo60, rhRo60,  and CFA, respectively.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2192918&req=5

Figure 6: Induction of ANAs following immunization with Ro60 antigens. Sera obtained on day 67, postimmunization, were pooled and used at a dilution of 1:200 to stain methanol-fixed HeLa cells (detected by indirect immunofluorescence). a, b, and c represent sera from mice immunized with rmRo60, rhRo60, and CFA, respectively.
Mentions: Sera from SJL mice immunized with rmRo60 and rhRo60 were positive for antinuclear antibodies (ANA) (Fig. 6, A and B, respectively). Although results are shown for pooled sera, all mice had ANA in their sera. Such antibodies were not detected in mice immunized with only CFA (Fig. 6 C).

Bottom Line: With human Ro60316-335 as the immunogen, additional autoantibodies reactive with the Golgi complex were found.These results show that both the nature of the immunogen and the immunogenicity of the related endogenous antigen are important in determining the specificities of the autoantibodies generated.They have significant implications for proposed mechanisms on the generation of complex patterns of autoantibodies to a diverse group of autoantigens in SLE patients.

View Article: PubMed Central - PubMed

Affiliation: Division of Rheumatology, Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.

ABSTRACT
Anti-Ro60 autoantibodies are found in a variety of autoimmune disorders including systemic lupus erythematosus (SLE), Sjögren's syndrome, primary biliary cirrhosis, and active hepatitis. They are the most prevalent autoantibodies in normal individuals and in asymptomatic mothers of infants afflicted with neonatal lupus. In the present study, immune responses to recombinant human Ro60 (rhRo60) and recombinant mouse Ro60 (rmRo60) and selected Ro60 peptides in non-SLE-prone mice were investigated. Multiple T and B cell epitopes were identified in Ro60. Immunizations with either xenogeneic or autologous Ro60 induced autoantibodies to a diverse group of autoantigens. In addition to La and Ro52, proteins in the small nuclear ribonucleoprotein (snRNP) particles such as SmA, SmB, SmD, and 70-kD U1-RNP were unexpectedly identified as targeted antigens. In the studies involving synthetic Ro60 peptides, both human and mouse Ro60316-335 peptides, which differ in three amino acids, were found to contain dominant cross-reactive T cell determinants. Immunizations with these peptides induced autoantibodies to Ro60, La, SmD, and 70-kD U1-RNP without autoantibodies to Ro52, SmA, or SmB. With human Ro60316-335 as the immunogen, additional autoantibodies reactive with the Golgi complex were found. In contrast to the immunodominance of both human and mouse Ro60316-335 peptides, the T cell determinant in human Ro60441-465 was dominant, whereas that in the mouse peptide was cryptic. Immunization with human Ro60441-465 induced primarily anti-peptide Abs. Mouse Ro60441-465 failed to induce an antibody response. These results show that both the nature of the immunogen and the immunogenicity of the related endogenous antigen are important in determining the specificities of the autoantibodies generated. They have significant implications for proposed mechanisms on the generation of complex patterns of autoantibodies to a diverse group of autoantigens in SLE patients.

Show MeSH
Related in: MedlinePlus