期刊
FRONTIERS IN IMMUNOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.631249
关键词
rheumatoid arthritis; cartilage oligomeric matrix protein; C57BL; 6 mice; T cell epitope; B cell epitope
类别
资金
- Swedish Research Council [2015-02662]
- Knut and Alice Wallenberg Foundation [KAM2015.0063]
- Swedish Foundation for Strategic Research [RB13-0156]
- Science and Technology Projects of Guangzhou [201707010365]
- Swedish Foundation for Strategic Research (SSF) [RB13-0156] Funding Source: Swedish Foundation for Strategic Research (SSF)
- Swedish Research Council [2015-02662] Funding Source: Swedish Research Council
A new model for rheumatoid arthritis has been established in C57BL/6 mice by immunization with human cartilage oligomeric matrix protein (COMP). This model is dependent on a COMP specific peptide binding A(b) and induces severe arthritis with high incidence in C57BL/6NJ (B6N) mice.
The most commonly used strains in experimental research, including genetically modified strains, are C57BL/6 mice. However, so far, no reliable model for rheumatoid arthritis is available, mainly due to the restriction by the MHC class II haplotype H-2(b). Collagen-induced arthritis (CIA) is the most widely used animal model of rheumatoid arthritis, but C57BL/6 strain is resistant to CIA because there is no collagen II peptide associated with H-2(b). To establish a rheumatoid arthritis model in C57BL/6 mice, we immunized C57BL/6NJ (B6N) mice with human cartilage oligomeric matrix protein (COMP), which induced severe arthritis with high incidence, accompanied by a strong auto-antibody response. Native COMP was required, as denatured COMP lost its ability to induce arthritis in B6N mice. An immunodominant COMP peptide was identified as the key T cell epitope, with a perfect fit into the A(b) class II peptide binding pocket. A critical amino acid in this peptide was found to be phenylalanine at position 95. Recombinant COMP mutated at position 95 (COMP_F95S) lost its ability to induce arthritis or a strong immune response in the B6N mice. In conclusion, A new model for RA has been established using C57BL/6 mice through immunization with COMP, which is dependent on a COMP specific peptide binding A(b), thus in similarity with CIA in A(q) expressing strains.
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