abstract |
Immunostimulatory compositions and methods comprising a DC immunoreceptor (DCIR) containing portion of ITIM to moderate potent cross-presentation are described herein. Human CD8 + T cell responses generated by targeting dendritic cell (DC) antigens were evaluated by means of several lectin receptors. A single exposure to a low dose of anti-DCIR-antigen conjugate initiated the immunity of C8D + antigen-specific T cell by all human DC subsets including DC generated in vivo, skin-isolated Langerhans cells and mDC and blood pDC. Enhanced specific CD8 + T cell responses were observed when antigens such as FluMP, MART-1, viral (HIV gag), etc., were administered to DC via DCIR, compared to those induced by a free antigen or antigen conjugated to a control mAb or administered via DC-SIGN, another lectin receptor. In addition, the Toll-like receptor (TLR) 7/8-agonist improved the cross presentation moderated by DCIR as well as in cross-priming. Thus, antigen targeting via the human DCIR receptor allows the activation of specific CD8 + T cell immunity. |