The crystal structure of the pathogenic collagen type II-specific mouse monoclonal antibody CIIC1 Fab: structure to function analysis.
Monoclonal anti-collagen type II antibody CIIC1 is an arthritogenic autoantibody, which induces arthritis in mice. We crystallized and solved the structure of CIIC1 Fab molecule. Analysis of structure revealed an interaction between the CDR regions of one Fab to the CH1 domain of another Fab, which resembles an antibody-antigen interaction. ELISA experiments confirmed the cross-reactivity of both the full CIIC1 antibody and a single chain Fv fragment to other anti-collagen antibodies which are of different isotypes and epitope specificity. The rheumatoid factor like reactivity of CIIC1 antibody together with its collagen type II specificity may explain the pathogenicity of this antibody.
Uysal
Hüseyin
H
Department of Molecular Biophysics, Lund University, Chemical Center, Box 124, SE 221 00, Lund, Sweden.
Sehnert
Bettina
B
Nandakumar
Kutty S
KS
Böiers
Ulrika
U
Burkhardt
Harald
H
Holmdahl
Rikard
R
Thunnissen
Marjolein M G M
MM
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D001323:Autoantibodies / Q000737:chemistry*; D024043:Collagen Type II / Q000737:chemistry*; D022801:Complementarity Determining Regions / Q000737:chemistry; D018360:Crystallography, X-Ray; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry; D006860:Hydrogen Bonding; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry*; D007074:Immunoglobulin G / Q000737:chemistry; D007135:Immunoglobulin Variable Region / Q000737:chemistry; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D055672:Static Electricity; D013329:Structure-Activity Relationship
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D024043:Collagen Type II; D022801:Complementarity Determining Regions; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007135:Immunoglobulin Variable Region