title: Functional Specialty of CD40 and Dendritic Cell Surface Lectins for Exogenous Antigen Presentation to CD8(+) and CD4(+) T Cells.
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.
authors.affiliation: Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA; Institute of Biomedical Studies, Baylor University, South 5th Street, Waco, TX 76706, USA.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Yin
authors.affiliation: Unité de Recherche sur les Maladies Infectieuses, Tropicales Emergentes, IRD 198, CNRS UMR7278, INSERM U1095, 27 bd Jean Moulin, 13385 Cedex 05, Marseille, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Gorvel
authors.affiliation: Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Zurawski
authors.affiliation: Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA.
authors.forename: Dapeng
authors.initials: D
authors.lastname: Li
authors.affiliation: Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Ni
authors.affiliation: Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Duluc
authors.affiliation: Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA; Institute of Biomedical Studies, Baylor University, South 5th Street, Waco, TX 76706, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Upchurch
authors.affiliation: Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA.
authors.forename: JongRok
authors.initials: J
authors.lastname: Kim
authors.affiliation: Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA; Institute of Biomedical Studies, Baylor University, South 5th Street, Waco, TX 76706, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Gu
authors.affiliation: Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Ouedraogo
authors.affiliation: Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA.
authors.forename: Yaming
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA; Institute of Biomedical Studies, Baylor University, South 5th Street, Waco, TX 76706, USA.
authors.forename: HyeMee
authors.initials: H
authors.lastname: Joo
authors.affiliation: CIML, Aix Marseille Université, CNRS UMR 7280, INSERM U1104, parc scientifique de Luminy, Case 906, Marseille, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gorvel
authors.affiliation: Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA; Institute of Biomedical Studies, Baylor University, South 5th Street, Waco, TX 76706, USA.
authors.forename: Gerard
authors.initials: G
authors.lastname: Zurawski
authors.affiliation: Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA; Institute of Biomedical Studies, Baylor University, South 5th Street, Waco, TX 76706, USA.
authors.forename: SangKon
authors.initials: S
authors.lastname: Oh
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D016233:Immunotherapy, Active; D037102:Lectins / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D011993:Recombinant Fusion Proteins / Q000276:immunology; D051127:Scavenger Receptors, Class E / Q000276:immunology; D000099181:Dectin-1
chemical_list: D023201:CD40 Ligand; D037102:Lectins; D037181:Lectins, C-Type; D011993:Recombinant Fusion Proteins; D051127:Scavenger Receptors, Class E; D000099181:Dectin-1; C495138:Olr1 protein, mouse
keywords: ANOVA, analysis of variance; AP, alkaline phosphatase; APC, antigen-presenting cells; CD, cluster of differentiation; CD40; CFSE, carboxyfluorescein succinimidyl ester; CTL, cytotoxic T lymphocyte; Coh, cohesin; Cross-presentation; DC, dendritic cell; Dendritic cell; Doc, dockerin; EEA1, early endosome antigen 1; ELISA, enzyme-linked immunosorbent assay; ELISpot, enzyme-linked immunospot; Flu.M1, influenza virus matrix protein 1; GM-CSF, granulocyte-macrophage colony-stimulating factor; HA1, hemagglutinin subunit 1; HLA, human leukocyte antigen; HPV, human papillomavirus; HRP, horseradish peroxidase; IFN, interferon; IL, interleukin; JaCoP, Just another Colocalization Plugin; LAMP-1, lysosomal-associated membrane protein 1; Lectins; MART-1, melanoma antigen recognized by T cells 1; MHC, major histocompatibility complex; Mo-DC, monocyte-derived dendritic cell; NHP, non-human primate; NP, nucleoprotein; PBMC, peripheral blood mononuclear cells; PBS, phosphate-buffered saline; PSA, prostate specific antigen; Poly(I:C), polyinosinic:polycytidylic acid; TLR, toll-like receptor; TMB, 3,3′,5,5′-tetramethylbenzidine; TNF, tumor necrosis factor; Vaccine; hCD40Tg, human CD40 transgenic; i.p., intraperitoneal(ly); mAb, monoclonal antibody; mDC, myeloid dendritic cell; pDC, plasmacytoid dendritic cell; s.c., subcutaneous(ly)