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…

By L. Bonifaz, D. Bonnyay, K. Mahnke, M. Rivera, Michel C. Nussenzweig, R. Steinman. Journal of Experimental Medicine, 2002

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To identify endocytic receptors that allow dendritic cells (DCs) to capture and present antigens on major histocompatibility complex (MHC) class I products in vivo, we evaluated DEC-205, which is abundant on DCs in lymphoid tissues. Ovalbumin (OVA) protein, when chemically coupled to monoclonal αDEC-205 antibody, was presented by CD11c+ lymph node DCs, but not by CD11c− cells, to OVA-specific, CD4+ and CD8+ T cells. Receptor-mediated presentation was at least 400 times more efficient than unconjugated OVA and, for MHC class I, the DCs had to express transporter of antigenic peptides (TAP) transporters. When αDEC-205:OVA was injected subcutaneously, OVA protein was identified over a 4–48 h period in DCs, primarily in the lymph nodes draining the injection site. In vivo, the OVA protein was selectively presented by DCs to TCR transgenic CD8+ cells, again at least 400 times more effectively than soluble OVA and in a TAP-dependent fashion. Targeting of αDEC-205:OVA to DCs in the steady state initially induced 4–7 cycles of T cell division, but the T cells were then deleted and the mice became specifically unresponsive to rechallenge with OVA in complete Freund's adjuvant. In contrast, simultaneous delivery of a DC maturation stimulus via CD40, together with αDEC-205:OVA, induced strong immunity. The CD8+ T cells responding in the presence of agonistic αCD40 antibody produced large amounts of interleukin 2 and interferon γ, acquired cytolytic function in vivo, emigrated in large numbers to the lung, and responded vigorously to OVA rechallenge. Therefore, DEC-205 provides an efficient receptor-based mechanism for DCs to process proteins for MHC class I presentation in vivo, leading to tolerance in the steady state and immunity after DC maturation.

Subfields: Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/67a98529bc1c7db55cb45e07d5bf91a317fb0b80

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Citations in the corpus

The perfect mix: recent progress in adjuvant research (2007, background): “Targeting this receptor in the absence of a maturation stimulus leads to CD8 + T-cell toleranc”
NOX2 controls phagosomal pH to regulate antigen processing during crosspresentation by dendritic cells. (2006, methodology): “aDEC205-OVA conjugates were produced and purified as described (Bonifaz et al., 2002).”
The Linkage of Innate to Adaptive Immunity via Maturing Dendritic Cells In Vivo Requires CD40 Ligation in Addition to Antigen Presentation and CD80/86 Costimulation (2004, background): “Instead, DCs in the steady state, or subsets of DCs, elicit different forms of peripheral tolerance, such as deletion (9, 10), anergy (12), and the expansion of regulatory T cells (13).”
In Vivo Targeting of Antigens to Maturing Dendritic Cells via the DEC-205 Receptor Improves T Cell Vaccination (2004, methodology): “at 25–50 g/mouse as described previously (20).”
DC-SIGN: escape mechanism for pathogens (2003, background): “Most C-type lectins that have a tri-acidic cluster (DEC205, DC-SIGN, BDCA2, dectin-1 and CLEC1) target internalized antigens to lysosomes and MHC class II-positive late endosome”
Dendritic cells: translating innate to adaptive immunity. (2006, background): “Relatively low doses of antigen often suffice for DCs to present antigens to T cells [69, 70, 92, 136].”