Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 380, Issue 3, Pages 715-720Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2009.01.157
Keywords
Osteopontin; Epitope; Monoclonal antibody; Lymphocyte migration
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Funding
- National Natural Science Foundation of China
- Shanghai Commission of Science and Technology
- E-Institutes of Shanghai Universities Immunology Division and Ministry of Science and Technology of China (973 and 863 Projects)
- Shanghai Pudong Bureau of Science and Technology of China
- Shanghai Commission of Education
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Osteopontin (OPN) plays an important role in regulating lymphocyte adhesion and cytokine production associated with inflammatory processes and autoimmune diseases. Here we developed and characterized a monoclonal antibody F8E11 specific for human OPN (hOPN). F8E11 could inhibit OPN-induced lymphocyte activation and migration. Epitope mapping showed that F8E11 could specifically recognize the peptide QLYxxYP. In addition, a synthesized mimetic peptide F8P (EEKQLYNKYPDA) could block the binding of F8E11 to hOPN and significantly inhibit the hOPN-induced lymphocyte migration. Moreover, mutations on the QLYxxYP motif of hOPN also markedly diminished its activity for lymphocyte activation and migration. The functioning assay indicated that this novel epitope is critically involved in the lymphocyte migration through activating MAPK/ERK/AP-1 pathway, which can be inhibited by the motif QLYxxYP blocking antibody, F8E11. These results Suggest that this novel epitope of OPN may provide a potential therapeutic target for the treatment of T cell mediated-immune diseases. (C) 2009 Elsevier Inc. All rights reserved.
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