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

Lahoud MH, Ahmet F, Kitsoulis S, Wan SS, Vremec D, Lee CN, Phipson B, Shi W, Smyth GK, Lew AM, Kato Y, Mueller SN, Davey GM, Heath WR, Shortman K, Caminschi I

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  • Journal Journal of immunology (Baltimore, Md. : 1950)

  • Published 15 Jun 2011

  • Volume 187

  • ISSUE 2

  • Pagination 842-50

  • DOI 10.4049/jimmunol.1101176

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.