Vaccination with an immunodominant peptide of bovine type II collagen induces an anti-TCR response, and modulates the onset and severity of collagen-induced arthritis.
T cell responses directed toward TCR-derived peptides have been shown to be an important regulatory mechanism of protection against autoimmunity. Here, we show that a naturally induced TCR-directed immune response can delay the onset of collagen-induced arthritis (CIA), an animal model of autoimmune rheumatoid arthritis in humans. DBA/1 mice were pretreated with an immunodominant peptide, p245-270, from bovine type II collagen (bCII) and were subsequently immunized with whole bCII for the induction of arthritis. The results showed that preactivation of p245-270-reactive cells delayed the onset and reduced the severity of CIA, compared with animals in the control group. Interestingly, the serum antibody response to bCII and the bCII-specific cytokine were not affected under these conditions. This result indicates that the observed protection was neither directly due to a lower antibody response nor due to the immune deviation of the anti-bCII T cell response. Furthermore, immunization with p245-270, but not bCII, induced a strong response to the B5 peptide, an immunodominant region of the TCR V(beta)8.2 (amino acids 76-101) that binds very strongly to I-A(q). These data suggest that at a critical phase in the loss of self-tolerance, an effective anti-TCR response, induced naturally, can regulate the pathogenic autoimmune response and thus may provide protection against autoimmunity.
Honda
Aki
A
Applied Biological Chemistry, University of Tokyo, Bunkyo, Tokyo 113-8650, Japan. aki@educ.cc.keio.ac.jp
Ametani
Akio
A
Matsumoto
Takashi
T
Iwaya
Amane
A
Kano
Hiroshi
H
Hachimura
Satoshi
S
Ohkawa
Kensuke
K
Kaminogawa
Shucihi
S
Suzuki
Koji
K
Sercarz
Eli E
EE
Kumar
Vipin
V
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001169:Arthritis, Experimental / Q000175:diagnosis / Q000276:immunology*; D001667:Binding, Competitive / Q000276:immunology; D002417:Cattle; D024043:Collagen Type II / Q000276:immunology*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology*; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008811:Mice, Inbred DBA; D010446:Peptide Fragments / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination
D000906:Antibodies; D024043:Collagen Type II; D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; C109168:T-cell receptor Vbeta 8.2; C493507:T-cell receptor Vbeta 8.2 (76-101); D007371:Interferon-gamma