Identification and characterization of a major tolerogenic T-cell epitope of type II collagen that suppresses arthritis in B10.RIII mice.
Tolerization of B10.RIII mice (H-2r) with intravenously injected type II collagen (CII) renders the animals resistant to induction of collagen-induced arthritis (CIA). In order to clarify H-2r-restricted T-cell responses that modulate CIA, we have analysed the T-cell proliferative response of B10.RIII mice against cyanogen bromide (CB) peptides of CII, and detected the strongest response to alpha 1(II)-CB10 (CII 552-897). A panel of chemically synthesized overlapping peptide homologues was used to deduce the minimum structure of this determinant which was found to be CII 610-618. A 15-residue synthetic peptide flanking this region, CII 607-621, was found to effectively suppress arthritis when administered as a tolerogen. Collectively, these data identify the structural component within alpha 1(II)-CB10 which is capable of inducing tolerance in B10.RIII mice. A similar approach to the treatment of autoimmune arthritis, involving the institution of self-tolerance, has potential applicability to human rheumatoid arthritis.
Miyahara
H
H
Department of Pediatrics, University of Tennessee, Memphis 38163, USA.
Myers
L K
LK
Rosloniec
E F
EF
Brand
D D
DD
Seyer
J M
JM
Stuart
J M
JM
Kang
A H
AH
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000097:blood; D001169:Arthritis, Experimental / Q000276:immunology* / Q000628:therapy; D003094:Collagen / Q000008:administration & dosage / Q000276:immunology*; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000302:isolation & purification*; D007108:Immune Tolerance; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology*
D000906:Antibodies; D018984:Epitopes, T-Lymphocyte; D003094:Collagen