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

First Author  Radhakrishnan S Year  2005
Journal  Proc Natl Acad Sci U S A Volume  102
Issue  32 Pages  11438-43
PubMed ID  16061819 Mgi Jnum  J:100468
Mgi Id  MGI:3588602 Doi  10.1073/pnas.0501420102
Citation  Radhakrishnan S, et al. (2005) B7-DC cross-linking restores antigen uptake and augments antigen-presenting cell function by matured dendritic cells (Retraction: PNAS 2010; 107(18): 8498). Proc Natl Acad Sci U S A 102(32):11438-43
abstractText  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.
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