Ras, leading to the activation of Raf-1 and the subsequent activation of MEK. The intracellular domain of OCILRP2 lacks the immunoreceptor tyrosine-based activation motif that triggers XAV939 lymphocyte activation, suggesting that OCILRP2 may transmit co-stimulatory signal via adaptors, such as DAP12, which interacts with NKG2D in activated NK cells and CD8+ T cells. DAP12 is a 12-kDa transmembrane protein that contains an aspartic acid residue in its transmembrane domain and a single cytoplasmic ITAM. DAP12 most likely activates SHC transforming protein 1 via the Syk-family protein-tyrosine kinase Zap-70. The sequential phosphorylation of the adaptors further triggers downstream signaling events, including the activation of the MAP and JNK kinases and nuclear translocation of transcription factors NF-AT, NF-kB, and AP-1, leading to IL-2 gene expression and T cell activation. Activated T cells also produce the alpha subunit of the IL-2 receptor, enabling a fully functional receptor that can bind with IL2, which in turn activates the T cell’s proliferation pathways. OCILRP2 is a type II transmembrane CTLR that is expressed in osteoblasts, B cells, dendritic cells, and activated T cells. Splenocytes derived from OCILRP2-Ig-treated mice show a significant reduction in proliferation and level of IL-2, and the addition of OCILRP2-Ig results in a dose-dependent inhibition of CD4+ T cell proliferation and IL-2 production, suggesting that OCILRP2 is required for splenocyte activation. The murine T cell line EL4 produces IL-2 in the presence of appropriate signals and provides a model system for analyzing T cell activation co-stimulated by H-2 and CD3 antibodies. JNK phosphorylation and c-jun transcription were found to be induced in EL4 cells in response to phorbol ester. The EL4 cell line has also been used to explore the roles of ERK activation in downstream responses. In this study, we confirmed that OCILRP2 co-stimulates T cell activation in mouse EL4 cells, and for the first time, we identify that an adaptor protein, DAP12, interacts with OCILRP2 and is involved in this T cell activation. Mechanistic studies revealed that the re-localization of OCILRP2 from the cytoplasm to the membrane under the stimulation of CD3/CD28 antibodies might be responsible for the observed T cell activation by activating the MAPK signal transduction pathway. These results provide novel insight into the mechanisms of T cell activation. In the present study, the costimulation of mouse T cell activation by the C-type lectin-like molecule OCILRP2 was confirmed in the EL4 cell line. In addition, OCILRP2 redistribution to the cell membrane and its interaction with the adaptor protein DAP12 was likely the cause of EL4 cell activation. Wenzhi Tian et al. first reported the effects of OCILRP2 on primary human T cell proliferation and IL-2 production. These authors found that silencing OCILRP2 leads to intrinsic defects in T cell survival as well as cell cycle progression in response to TCR and CD28 signaling. Recently, further studies on the possible mechanism of T cell activation have been reported. Thebault P et al. demonstrated that the C-type lectin-like receptor CLEC-1.