Preferential Induction of CD4+ T Cell Responses through In Vivo Targeting of Antigen to Dendritic Cell-Associated C-Type Lectin-1
- 15 August 2006
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 177 (4), 2276-2284
- https://doi.org/10.4049/jimmunol.177.4.2276
Abstract
Targeting of Ags and therapeutics to dendritic cells (DCs) has immense potential for immunotherapy and vaccination. Because DCs are heterogeneous, optimal targeting strategies will require knowledge about functional specialization among DC subpopulations and identification of molecules for targeting appropriate DCs. We characterized the expression of a fungal recognition receptor, DC-associated C-type lectin-1 (Dectin-1), on mouse DC subpopulations and investigated the ability of an anti-Dectin-1 Ab to deliver Ag for the stimulation of immune responses. Dectin-1 was shown to be expressed on CD8α−CD4−CD11b+ DCs found in spleen and lymph nodes and dermal DCs present in skin and s.c. lymph nodes. Injection of Ag-anti-Dectin-1 conjugates induced CD4+ and CD8+ T cell and Ab responses at low doses where free Ag failed to elicit a response. Notably, qualitatively different immune responses were generated by targeting Ag to Dectin-1 vs CD205, a molecule expressed on CD8α+CD4−CD11b− DCs, dermal DCs, and Langerhans cells. Unlike anti-Dectin-1, anti-CD205 conjugates failed to elicit an Ab response. Moreover, when conjugates were injected i.v., anti-Dectin-1 stimulated a much stronger CD4+ T cell response and a much weaker CD8+ T cell response than anti-CD205. The results reveal Dectin-1 as a potential targeting molecule for immunization and have implications for the specialization of DC subpopulations.Keywords
This publication has 51 references indexed in Scilit:
- The Beta-Glucan Receptor Dectin-1 Recognizes Specific Morphologies of Aspergillus fumigatusPLoS Pathogens, 2005
- Effective induction of naive and recall T-cell responses by targeting antigen to human dendritic cells via a humanized anti–DC-SIGN antibodyBlood, 2005
- A role for fungal β-glucans and their receptor Dectin-1 in the induction of autoimmune arthritis in genetically susceptible miceThe Journal of Experimental Medicine, 2005
- Dectin-1 uses novel mechanisms for yeast phagocytosis in macrophagesBlood, 2004
- Efficient Targeting of Protein Antigen to the Dendritic Cell Receptor DEC-205 in the Steady State Leads to Antigen Presentation on Major Histocompatibility Complex Class I Products and Peripheral CD8+ T Cell ToleranceThe Journal of Experimental Medicine, 2002
- The CD8α+ Dendritic Cell Is Responsible for Inducing Peripheral Self-Tolerance to Tissue-associated AntigensThe Journal of Experimental Medicine, 2002
- Dectin-1 Is A Major β-Glucan Receptor On MacrophagesThe Journal of Experimental Medicine, 2002
- C-type lectin receptors on dendritic cells and langerhans cellsNature Reviews Immunology, 2002
- Dendritic Cells Induce Peripheral T Cell Unresponsiveness under Steady State Conditions in VivoThe Journal of Experimental Medicine, 2001
- Adjuvant-free IgG responses induced with antigen coupled to antibodies against class II MHCNature, 1987