Silencing OCILRP2 leads to intrinsic defects in T cells in response to antigenic stimulation.
We have previously demonstrated that OCILRP2 interaction with its ligand NKRP1f provides a co-stimulatory signal for optimal T cell proliferation and IL-2 production. Here, using RNA interference technology, we will demonstrate that silencing OCILRP2 in vivo leads to intrinsic impairment in T cell response to CD3- and CD28-cross-linking as well as antigenic stimulation. OCILRP2-silenced T cells have reduced cell proliferation and IL-2 production, which can be bypassed by PMA and ionomycin treatment. OCILRP2-silenced T cells also failed to undergo TCR capping and had impaired cytoskeleton reorganization. Moreover, in OCILRP2-silenced T cells, tyrosine phosphorylation of Lck was diminished, while tyrosine phosphorylation of linkers for activation of T cells was unchanged. Interestingly, NF-kappaB activation was also impaired as the result of OCILRP2 silencing. Together, our data strongly support a novel role for OCILRP2 C-type lectin in TCR-mediated signal transduction. The observation that OCILRP2 is involved in TCR capping and cytoskeletal organization suggests that OCILRP2-NKRP1f may facilitate lipid rafts and immunological synapse formation during T cell interaction with antigen presenting cells.
Tian
Wenzhi
W
Division of Immunology, Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.
Feng
Biao
B
Liou
Hsiou-Chi
HC
D000818:Animals; D000941:Antigens; D016026:Bone Marrow Transplantation; D019070:Cell Lineage / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D005260:Female; D020868:Gene Silencing; D007376:Interleukin-2 / Q000378:metabolism; D037181:Lectins, C-Type / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D021962:Membrane Microdomains / Q000276:immunology; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D034622:RNA Interference; D034741:RNA, Small Interfering; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
D000941:Antigens; C470572:Dcl1 protein, mouse; D007376:Interleukin-2; D037181:Lectins, C-Type; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D011948:Receptors, Antigen, T-Cell