A functional motif QLYxxYP is essential for osteopontin induced T lymphocyte activation and migration.
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.
Dai
Jianxin
J
International Joint Cancer Institute, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China.
Cao
Zhiguo
Z
Kang
Yanshen
Y
Fan
Kexing
K
Ji
Guanghui
G
Yang
Haiou
H
Wang
Huajing
H
Gao
Jie
J
Wang
Hao
H
Guo
Yajun
Y
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D002465:Cell Movement; D018604:Epitope Mapping; D006801:Humans; D008213:Lymphocyte Activation; D018716:Molecular Mimicry; D009154:Mutation; D009842:Oligopeptides / Q000737:chemistry / Q000276:immunology; D053495:Osteopontin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D009842:Oligopeptides; D053495:Osteopontin