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Collagen antibody-induced arthritis in mice: Development of a new arthritogenic 5-clone cocktail of monoclonal anti-type II collagen antibodies |
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| Authors: | Pilaiwanwadee Hutamekalin Kouya Yamaki David D. Brand Kuniaki Terato |
| Affiliation: | a Department of Pharmacology, Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Higashinada-ku, Kobe-shi, Hyogo-ken, 658-8558, Japan b Research Service, Veterans Affairs Medical Center, Memphis, TN, USA c Chondrex Incorporated, 2607 151st Place NE, Redmond, WA 98052, USA |
| Abstract: | A cocktail of 4 monoclonal anti-type II collagen antibodies recognizing conserved epitopes located within the CB11 fragment (CII 124-402) of type II collagen is currently used as an arthritogenic antibody preparation for inducing collagen antibody induced arthritis (CAIA). In order to increase the arthritogenicity of this cocktail, we have developed 7 new monoclonal antibodies to anti-type II collagen from spleen cells of DBA/1J mice immunized with bovine type II collagen, and tested for their additional effect on the arthritogenicity over that of the current 4-clone cocktail. Three of the clones (CII-3, -5 and -6) bind to the LyC1 (CII 124-290) peptide of CB11 and 1 (CII-7) of the clones binds to CB9.7 (CII 898-1020), and highly cross-reacted with other species of type II collagen. This indicates that these clones recognize conserved epitopes within type II collagen, including mouse type II collagen. On the other hand, 2 other clones (CII-1 and -4) directed against CB9.7 and 1 clone (CII-2) against CB8 (CII 403-551) were less reactive with other species of type II collagen.The arthritogenicity of the current 4-clone cocktail was significantly increased by addition of a fifth clone, CII-3. No effects were observed with other clones. The arthritogenicity of this new 5-clone cocktail was 2-fold greater than the current 4-clone cocktail in all strains of mice tested: the CIA-responder strain DBA/1J, the CIA-resistant BALB/c (H-2d), the T-cell deficient C.B-17/l scid/scid and the CAIA-low responder C57BL/6 (H-2b) strain. These results clearly indicated the importance of epitope specificity of arthritogenicity of autoantibodies to type II collagen. Due to its enhanced arthritogenicity, this 5-clone cocktail is capable of inducing a more consistent and severe arthritis with lower doses compared to the current 4-clone cocktail, and will provide an effective new reagent for inducing arthritis in various strains of CAIA low responder mice. |
| Keywords: | CIA, collagen arthritis CB11, CNBr-digest fragment number 11 CAIA, collagen antibody-induced arthritis |
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