Diversity of the immune response to bovine type II and XI collagens in rats.

Immunisation of rats with native type II or type XI collagen produced an inflammatory arthritis in certain strains of rats. Antibodies to the native and denatured whole molecules, to the individual alpha chains and to the cyanogen bromide derived peptides of these chains were studied. Inter- and intra-strain variation in the specificity of the antibodies produced was seen and there were also changes with time, especially with the rats immunised with type XI collagen. Both collagen type-specific and cross-reacting antibodies were produced following immunisation with either type II or type XI collagen. Although no specific pattern of antibodies was unique to the presence or absence of arthritis in all rats, antibodies that bound to the CB-11 peptide or antibodies that bound to the CB-9,7 peptide of type II collagen occurred at the time of onset of arthritis in type II or type XI immunised, arthritic rats. Antibodies to these peptides occur in many patients with rheumatoid arthritis (RA) who also have antibodies to type II collagen. Therefore these findings suggest that epitopes on these peptides may be important in the continued production of antibodies to these collagens in patients with RA and that these antibodies may indeed be pathogenic.