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

MH Lahoud, F Ahmet, S Kitsoulis, SS Wan… - The Journal of …, 2011 - journals.aai.org
MH Lahoud, F Ahmet, S Kitsoulis, SS Wan, D Vremec, CN Lee, B Phipson, W Shi, GK Smyth
The Journal of Immunology, 2011journals.aai.org
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 …
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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