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Immunization with peptides from 60 kDa Ro in diverse mouse strains
R H Scofield1, P G Pierce, J A James
1Arthritis 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. hal-scofield@omrf.ouhsc.edu
Scandinavian Journal of Immunology
|November 2, 2002
Summary
Autoantibodies to Ro (or SSA) and La (or SBB) proteins are linked to autoimmune diseases. Ro peptide immunization in mice shows that genetic variations influence the immune response and epitope spreading, impacting autoantibody development.
Area of Science:
- Immunology
- Autoimmunity
- Genetics
Background:
- Ro (or SSA) and La (or SBB) autoantibodies are prevalent in systemic lupus erythematosus and Sjögren's syndrome.
- The mechanisms driving the development of these autoantibodies remain unclear.
- Previous studies demonstrated that Ro ribonucleoprotein particle peptide immunization can induce autoimmunity and epitope spreading in mice.
Purpose of the Study:
- To investigate the influence of genetic background on epitope spreading following Ro peptide immunization.
- To compare the immune response diversity across different mouse strains after immunization with a specific 60 kDa Ro peptide.
Main Methods:
- Immunization of different mouse strains (DBA/2J, C57Bl/6J, PL/J) with a monomer peptide (residues 480-494) from the 60 kDa Ro protein.
- Analysis of autoantibody production, including binding to various Ro protein epitopes, 52 kDa Ro, and La protein.
- Assessment of antinuclear antibody presence in sera.
Main Results:
- DBA/2J mice exhibited intra- and intermolecular immune response diversification, developing antibodies to multiple 60 kDa Ro epitopes, 52 kDa Ro, and La.
- The immunizing peptide did not induce epitope spreading in C57Bl/6J or PL/J mice.
- DBA/2J mice developed antinuclear antibodies, similar to previously studied BALB/c mice.
Conclusions:
- Ro peptide immunization leads to strain-dependent variations in immune response outcomes and epitope spreading.
- Genetic background plays a crucial role in determining the extent and nature of epitope spreading following peptide immunization.
- These findings highlight the importance of host genetics in the development of autoantibody responses.