International Immunology Advance Access originally published online on March 29, 2004
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International Immunology, Vol. 16, No. 5, pp. 737-745,
May 2004
© 2004 Japanese Society for Immunology
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
1 Applied Biological Chemistry, University of Tokyo, Bunkyo, Tokyo 113-8650, Japan 2 Applied Chemistry, Keio University, Yokohama, Kanagawa 223-8582, Japan 3 Japan Science and Technology Agency, CREST, Kawaguchi, Saitama 332-0012, Japan 4 Research and Development Center, Nippon Meat Packers, Tsukuba, Ibaraki 300-2646, Japan 5 Immune Regulation, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA
Correspondence to: A. Honda; E-mail: aki{at}educ.cc.keio.ac.jp
Transmitting editor: K. Okumura
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 Vß8.2 (amino acids 76–101) that binds very strongly to I-Aq. 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.
Keywords: anti-TCR response, collagen-induced arthritis, immune regulation
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