B7-DC cross-linking restores antigen uptake and augments antigen-presenting cell function by matured dendritic cells.
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.
Radhakrishnan
Suresh
S
Department of Immunology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
Celis
Esteban
E
Pease
Larry R
LR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017951:Antigen Presentation / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism*; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D005434:Flow Cytometry; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D061027:Programmed Cell Death 1 Ligand 2 Protein
D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; C556978:Pdcd1lg2 protein, mouse; D061027:Programmed Cell Death 1 Ligand 2 Protein