title: The C-type lectin OCILRP2 costimulates EL4 T cell activation via the DAP12-Raf-MAP kinase pathway.
abstract: OCILRP2 is a typical Type-II transmembrane protein that is selectively expressed in activated T lymphocytes, dendritic cells, and B cells and functions as a novel co-stimulator of T cell activation. However, the signaling pathways underlying OCILRP2 in T cell activation are still not completely understood. In this study, we found that the knockdown of OCILRP2 expression with shRNA or the blockage of its activity by an anti-OCILRP2 antagonist antibody reduced CD3/CD28-costimulated EL4 T cell viability and IL-2 production, inhibit Raf1, MAPK3, and MAPK8 activation, and impair NFAT and NF-κB transcriptional activities. Furthermore, immunoprecipitation results indicated that OCILRP2 could interact with the DAP12 protein, an adaptor containing an intracellular ITAM motif that can transduce signals to induce MAP kinase activation for T cell activation. Our data reveal that after binding with DAP12, OCILRP2 activates the Raf-MAP kinase pathways, resulting in T cell activation.
authors.affiliation: Henan Engineering Lab of Antibody Medicine, Key Laboratory of Cellular and Molecular Immunology, Medical College of Henan University, Kaifeng 475004, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lou
authors.affiliation: Henan Engineering Lab of Antibody Medicine, Key Laboratory of Cellular and Molecular Immunology, Medical College of Henan University, Kaifeng 475004, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Henan Engineering Lab of Antibody Medicine, Key Laboratory of Cellular and Molecular Immunology, Medical College of Henan University, Kaifeng 475004, China.
authors.forename: Guangchao
authors.initials: G
authors.lastname: Liu
authors.affiliation: Henan Engineering Lab of Antibody Medicine, Key Laboratory of Cellular and Molecular Immunology, Medical College of Henan University, Kaifeng 475004, China.
authors.forename: Yuanfang
authors.initials: Y
authors.lastname: Ma
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D000906:Antibodies / Q000378:metabolism; D018106:CD28 Antigens / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D007376:Interleukin-2 / Q000378:metabolism; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D008213:Lymphocyte Activation; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies; D018106:CD28 Antigens; D017252:CD3 Complex; C470572:Dcl1 protein, mouse; D007376:Interleukin-2; D037181:Lectins, C-Type; D008565:Membrane Proteins; C484963:Tyrobp protein, mouse; D019908:Proto-Oncogene Proteins c-raf