In the presence of anti-CD40, CTLs are primed in vivo and prevent OVA+ expressing tumor cell growth [146]. Injection of anti-DNGR-1 monoclonal antibody-OVA conjugate into mice was Icotinib purchase endocytozed by CD8+ DCs, presented antigen to CD4+ T cells, and played a major role in the differentiation of CD4+ T cells into Foxp3+ regulatory T cells [147]. The addition of the adjuvant poly I:C enhanced IL-12 mediated immunity, whereas the adjuvant curdlan primed Th17 cells [147]. In addition, vaccinia virus infected dying cells are endocytozed by DNGR-1 on DCs and mediate cross-priming of antivaccinia virus infected cell

CD8+ T-cell responses; loss of DNGR-1 impairs CD8+ CTL responses [148, 149]. Thus, Inhibitors,research,lifescience,medical DNGR-1 regulates cross-presentation of viral antigens and could be further assessed as a target for vaccination protocols. Furthermore, a single injection of anti-Clec9A monoclonal antibody induced striking antibody and Inhibitors,research,lifescience,medical CD4+ T cells responses in the absence

of adjuvant or danger signals in mice and in TLR knockout mice [150, 151]. Targeting antigens to Clec9A shows promise to enhance vaccine efficiency; indeed, anti-Clec9A monoclonal antibody conjugated to HIV gag-p24 induced strong Th1 and CD8+ T-cell responses in mice [123]. DNGR-1/Clec9A could prove useful for developing immunotherapy protocols Inhibitors,research,lifescience,medical for cancer and other diseases. MICL. MICL (myeloid inhibitory C-type lectin-like receptor, Clec12A) is homologous to Inhibitors,research,lifescience,medical Dectin-1 and is part of the Dectin-1 cluster [152]. Numerous other groups identified this receptor and named it C-type lectin-like molecule-1 (CLL-1), DC associated C-type lectin 2 (DCAL-2), and killer

cell lectin-like receptor 1 (KLRL1) [153–155]. MICL is expressed on granulocytes, monocytes, macrophages, B cells, CD8+ T cells in peripheral blood, and DCs (Table 1) [156], and, contains a tyrosine based inhibitory motif in its cytoplasmic tail, similar to lectin-like Inhibitors,research,lifescience,medical receptor for oxidized density lipoprotein-1 (LOX-1) and Dectin-1, and can inhibit cellular activation. Hence, MICL is a negative regulator of granulocytes and monocytes [152]. MICL has a range of functions including cell adhesion, cell-cell signaling, turnover of glycoproteins, and in inflammation and in immune responses. CLEC2. CLEC2 (also known as Clec1B), a C-type lectin-like receptor 2, is expressed why on NK cells, DCs, monocytes, granulocytes, platelets, megakaryocytes, and liver sinusoidal endothelial cells (Table 1) [157]. CLEC2 is a platelet activation receptor for the endogenous ligand, podoplanin (a mucin-like sialoglycoprotein) expressed on a number of cells including lymphatic endothelial cells and implicated in cancer cell metastasis [158]. CLEC2 on platelets binds to HIV-1 and facilitates HIV-1 spread to other immune cells. The binding of HIV-1 to platelets via CLEC2 is highly dependent on DC-SIGN, suggesting that the two coexist [159]. In addition, the snake venom rhodocytin binds to CLEC2 on platelets and activates cell signaling [160].