Chick
type II collagen (CII), a
protein commonly found in joint cartilage, induces an autoimmune
arthritis when administered to susceptible strains of mice. A
cyanogen bromide fragment of CII, CB11, contains the requisite
epitopes critical for inducing
collagen-induced arthritis. If administered as a
tolerogen, however, before immunization, CB11 prevents the onset of disease. Therefore, delineation of structural elements of CB11 that can regulate autoreactive T cells became the goal of this study. To delineate the structural elements of CB11 antigenic to T cells, 14
peptides containing overlapping sequences of CB11 were generated. Mononuclear cells from CII-immunized DBA/1 mice were cultured with these
peptides and the resulting supernatants examined for the production of IFN-gamma. Two
peptides, CII 181-209 and CII 245-270, generated the greatest responses. The ability of these two
peptides to regulate
arthritis was tested by administering them to neonatal DBA/1 mice as tolerogens before immunization with CII. Both
peptides suppressed the incidence of
arthritis whereas no other
peptide used as a
tolerogen significantly altered the course of the disease. T cells from four
arthritis-resistant murine strains did not recognize either
peptide when immunized with CII, whereas cells from the disease-susceptible B10.Q mice responded well to both. Thus, the coincidence of T cell responses to CII 181-209 and CII 245-270 in CIA-susceptible mice and the lack of response in disease-resistant strains or CII-tolerized mice identify these two
peptides as containing important
T cell epitopes that regulate CIA.