We have previously reported that
collagen-induced arthritis can be suppressed by
intravenous injection of native type II (CII) but not
type I collagen. We have now identified denatured fragments of CII capable of suppressing
collagen-induced arthritis and inducing tolerance. Purified CII was cleaved with
cyanogen bromide (CB), and the major resulting
peptides were isolated. Female DBA/1 mice were administered OVA, native CII, or one of the CB
peptides, intravenously, before immunization with native CII, 6 wk after immunization, mice tolerized with CII and CB11 had a markedly lower incidence of
arthritis compared with controls. There was a correlation between the overall antibody response and the incidence of
arthritis. In addition, animals tolerized with either CII or CB11 had a decreased antibody response not only to CII, but also to each of the other CB
peptides tested. To identify the
epitope involved in suppression of
arthritis, five synthetic
peptides, 21-26
amino acids in length, corresponding to selected regions of CB11, were generated. Each of the
peptides was injected intravenously into mice before immunization. Only one of these, CB11 122-147, was capable of suppressing
arthritis. In addition, mice given the synthetic
peptide CB11 122-147 neonatally were suppressed for
arthritis and antibody responsiveness when immunized with CII at 8 wk of age. Thus, we have identified CB11 122-147 as an
epitope of CII important in induction of tolerance and suppression of disease. Further experiments narrowing down the pivotal
amino acids for the immunogenicity of this
epitope and the role this
epitope plays in induction and regulation of disease will enhance our understanding of how the immune response to
collagen affects autoimmune
arthritis.