Epitope specific antibody response against human type II collagen induced by anti-idiotypic antibody

Abstract

A species specific epitope on human type II collagen (CII) recognized with mAb, 2-60, was found to be localized on a cyanogen bromide-cleaved peptide (CB10) of human CII. To characterize the antibody response to the 2-60 epitope, we raised rabbit anti-idiotypic (Id) antibody against 2-60. The rabbit anti-2-60 Id antibody reacted not only with 2-60 mAb but also with 2-56 and 3-11 mAbs which were reactive with the epitopes related to the 2-60 epitope on CB10. The anti-Id antibody inhibited the binding of these three mAbs to human CII. Thus, rabbit anti-2-60 Id antibody recognized the cross-reactive idiotype expressed on 2-60, 2-56 and 3-11. The anti-2-60 Id antibody inhibited about thirty percent of the binding of polyclonal anti-human CII antibody derived from DBA/1J mice, thereby suggesting that the 2-60 idiotype might be expressed on a major fraction of the anti-human CII antibody. Immunization with the rabbit anti-2-60 Id antibody elicited antibody response to the 2-60 epitope, in DBA/1J (H-2q, Ighc), BALB/c (H-2d, Igha) and DBA/2 (H-2d, Ighc) mice. On the other hand, an epitope-specific antibody response induced by rabbit anti-Id antibody to 1-5 mAb reactive with a putative arthritogenic epitope on human CII was shown to be influenced by a single dominant gene, possibly the Igh gene. Our findings suggest that antibody responses against two distinct epitopes on human CII are probably regulated by different mechanisms.