Targeting antigen to mouse dendritic cells via Clec9A induces potent CD4 T cell responses biased toward a follicular helper phenotype

通过 Clec9A 将抗原靶向小鼠树突状细胞可诱导出偏向滤泡辅助表型的强效 CD4 T 细胞反应

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作者:Mireille H Lahoud, Fatma Ahmet, Susie Kitsoulis, Soo San Wan, David Vremec, Chin-Nien Lee, Belinda Phipson, Wei Shi, Gordon K Smyth, Andrew M Lew, Yu Kato, Scott N Mueller, Gayle M Davey, William R Heath, Ken Shortman, Irina Caminschi

Abstract

Three surface molecules of mouse CD8(+) dendritic cells (DCs), also found on the equivalent human DC subpopulation, were compared as targets for Ab-mediated delivery of Ags, a developing strategy for vaccination. For the production of cytotoxic T cells, DEC-205 and Clec9A, but not Clec12A, were effective targets, although only in the presence of adjuvants. For Ab production, however, Clec9A excelled as a target, even in the absence of adjuvant. Potent humoral immunity was a result of the highly specific expression of Clec9A on DCs, which allowed longer residence of targeting Abs in the bloodstream, prolonged DC Ag presentation, and extended CD4 T cell proliferation, all of which drove highly efficient development of follicular helper T cells. Because Clec9A shows a similar expression pattern on human DCs, it has particular promise as a target for vaccines of human application.

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