Functional Specialty of CD40 and Dendritic Cell Surface Lectins for Exogenous Antigen Presentation to CD8+ and CD4+ T Cells

Wenjie Yin, Laurent Gorvel, Sandra Zurawski, Dapeng Li, Ling Ni, Dorothée Duluc, Katherine Upchurch, Jong Rok Kim, Chao Gu, Richard Ouedraogo, Zhiqing Wang, Yaming Xue, HyeMee Joo, Jean Pierre Gorvel, Gerard Zurawski, SangKon Oh

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Dendritic cells (DCs) are major antigen-presenting cells that can efficiently prime and cross-prime antigen-specific T cells. Delivering antigen to DCs via surface receptors is thus an appealing strategy to evoke cellular immunity. Nonetheless, which DC surface receptor to target to yield the optimal CD8+ and CD4+ T cell responses remains elusive. Herein, we report the superiority of CD40 over 9 different lectins and scavenger receptors at evoking antigen-specific CD8+ T cell responses. However, lectins (e.g., LOX-1 and Dectin-1) were more efficient than CD40 at eliciting CD4+ T cell responses. Common and distinct patterns of subcellular and intracellular localization of receptor-bound αCD40, αLOX-1 and αDectin-1 further support their functional specialization at enhancing antigen presentation to either CD8+ or CD4+ T cells. Lastly, we demonstrate that antigen targeting to CD40 can evoke potent antigen-specific CD8+ T cell responses in human CD40 transgenic mice. This study provides fundamental information for the rational design of vaccines against cancers and viral infections.

Original languageEnglish (US)
Pages (from-to)46-58
Number of pages13
JournalEBioMedicine
Volume5
DOIs
StatePublished - Mar 1 2016
Externally publishedYes

Keywords

  • CD40
  • Cross-presentation
  • Dendritic cell
  • Lectins
  • Vaccine

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Yin, W., Gorvel, L., Zurawski, S., Li, D., Ni, L., Duluc, D., Upchurch, K., Kim, J. R., Gu, C., Ouedraogo, R., Wang, Z., Xue, Y., Joo, H., Gorvel, J. P., Zurawski, G., & Oh, S. (2016). Functional Specialty of CD40 and Dendritic Cell Surface Lectins for Exogenous Antigen Presentation to CD8+ and CD4+ T Cells. EBioMedicine, 5, 46-58. https://doi.org/10.1016/j.ebiom.2016.01.029