T cell epitopes of type II collagen that regulate murine collagen-induced arthritis.
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.
Myers
L K
LK
Department of Pediatrics, University of Tennessee, Memphis 38163.
Seyer
J M
JM
Stuart
J M
JM
Terato
K
K
David
C S
CS
Kang
A H
AH
D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology; D001168:Arthritis / Q000276:immunology*; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D003094:Collagen / Q000276:immunology*; D000939:Epitopes; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology*
D001324:Autoantigens; D000939:Epitopes; D003094:Collagen