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DENDRITIC CELL IMMUNORECEPTORS (DCIR)-MEDIATED CROSSPRIMING OF HUMAN CD8+ T CELLS
DENDRITIC CELL IMMUNORECEPTORS (DCIR)-MEDIATED CROSSPRIMING OF HUMAN CD8+ T CELLS
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机译:树突状细胞免疫受体(DCIR)介导的人类CD8 + T细胞交叉杂交
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摘要
Immunostimulatory compositions and methods comprising an ITIM motif-containing DC immunoreceptor (DCIR) to mediate potent crosspresentation are described herein. The inventors evaluated human CD8+ T cell responses generated by targeting antigens to dendritic cells (DCs) through various lectin receptors. A single exposure to a low dose of anti-DCIR-antigen conjugate initiated antigen-specific CD8+ T cell immunity by all human DC subsets including ex vivo generated DCs, skin-isolated Langerhans cells and blood mDCs and pDCs. Enhanced specific CD8+ T cell responses were observed when antigens like, FluMP, MART-1, viral (HIV gag), etc. were delivered to the DCs via DCIR, compared to those induced by a free antigen, or antigen conjugated to a control mAb or delivered via DC-SIGN, another lectin receptor. Addition of Toll-like receptor (TLR) 7/8-agonist enhanced DCIR-mediated crosspresentation as well as crosspriming. Thus, antigen targeting via the human DCIR receptor allows activation of specific CD8+ T cell immunity.
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