Targeting antigens to DCIR were evaluated for their potential to stimulate CD8+ T-cell responses. Anti-DCIR monoclonal antibody linked to influenza matrix protein, melanoma antigen
MART-1, or to HIV gag antigens resulted in expansion of CD8+ T cells in vitro [169] and stimulation of Th1 and CD8+ T cells in vivo [123]. The addition of TLR-7/8 agonists enhanced T expansion of primed CD8+ T cells and induced the Kinase Inhibitor Library cell line production of IFN-gamma and TNF-alpha and reduced the levels of Th2 cytokines [169]. It is clear that, antigen targeting via the DCIR activates specific CD8+ T-cell Inhibitors,research,lifescience,medical immune responses. Dectin-2. Dectin-2 (or DCAL-2, Clec6A) or beta-glucan receptor is a C-type lectin receptor expressed on DCs, macrophages, neutrophils, and monocytes (Table 1) [170]. Dectin-2 is a receptor for beta-glucan recognizing beta1,3 and beta1,6-linked Inhibitors,research,lifescience,medical glucans on yeast, mycobacterial, and plant cell walls and plays a role in innate immune responses [137, 138]. Anti-Dectin-2 monoclonal antibody conjugated to antigen Inhibitors,research,lifescience,medical stimulate, CD8+ T cells in mice [142]. In addition, a lentivector using the mouse Dectin-2 gene promoter, was taken up by bone marrow derived DCs, Langerhans cells, and dermal DCs in vitro [171]. The Dectin-2 lentivector encoding the human melanoma antigen, NY-ESO-1, stimulated CD4+ and CD8+ T cells in mice [171]. Thus, Dectin-2
Inhibitors,research,lifescience,medical expressed on DCs is a potential targeting protein for vaccinations. BDCA-2. Blood DC antigen 2 (BDCA-2, Clec4C) is a type II C-type lectin expressed on human blood DCs, which has 57% homology with its murine homolog Dectin-2. Anti-BDCA-2 monoclonal antibody is rapidly internalized by plasmacytoid DCs and presented to T cells and suppresses the induction of IFN-alpha/beta cytokine secretion [172]. 3. DEC205
DEC-205 (CD205 or lymphocyte antigen Ly 75) is a type-I integral membrane protein homologous to the macrophage MR family of C-type lectins, which binds carbohydrates and mediates endocytosis (Figure 1) [173]. Inhibitors,research,lifescience,medical DEC-205 is primarily expressed on DCs and thymic epithelial cells. DEC205 mediates a number of different biological functions, such as binding and internalization of ligands Rutecarpine for processing and presentation by DCs (Table 2). Although the ligands which bind to DEC205 are not clear, following ligand binding, DEC-205 is rapidly internalized by means of coated pits and vesicles and is delivered to multivesicular endosomal compartments that resemble the MHC class II-containing vesicles implicated in antigen presentation. Due to the endocytic properties of DEC205, it is a promising receptor for antigen delivery for vaccines and targeted immunotherapies [174]. Upon DC maturation, DEC205 is upregulated, unlike other members of the macrophage MR family.