B7-DC cross-linking restores antigen uptake and augments antigen-presenting cell function by matured dendritic cells

Suresh Radhakrishnan, Esteban Cells, Larry R. Pease

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Dendritic cells (DCs) are classified in two states: immature DCs (iDCs), which perform sentinel functions, sampling for antigen and danger signals, and mature DCs (mDCs), which exhibit enhanced antigen-presenting functions but are no longer capable of acquiring antigen. We now describe DCs with a different activation phenotype: cells having the strong antigen-presenting functions of mDCs and the antigen-acquiring functions of iDCs. We have described an antibody that binds the costimulatory molecule B7-DC and activates DCs. The resulting phenotype is distinct from iDCs or mDCs matured by using Toll-like receptor (TLR) agonists. Ability to take up antigen increases, while expression of B71 2 costimulatory and MHC molecules remains unchanged. DCs matured with TLR agonists and then superactivated through B7-DC exhibit a previously unrecognized phenotype. These DCs recover the ability to take up antigen, which is normally lost after treatment with TLR-3 and TLR-9 agonists, yet retain the high expression of costimulatory and MHC molecules and strong antigen-presenting functions of mDCs. Immunization using TLR agonists and B7-DC XAb (cross-linking antibody) together as adjuvant resulted in substantially increased cytolytic T cell responses, particularly when minimal peptide antigens were used. By stimulating DCs with two distinct activation signals, a previously unrecognized phenotype exhibiting augmented antigen-presenting functions was obtained.

Original languageEnglish (US)
Pages (from-to)11438-11443
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number32
DOIs
StatePublished - Aug 9 2005

Keywords

  • Costimulation
  • Cytotoxic T cells
  • IgM
  • PD-L2
  • Synergy

ASJC Scopus subject areas

  • General

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