Conventional type 1 dendritic cells induce T_H1, T_H1‐like follicular helper T cells and regulatory T cells after antigen boost via DEC205 receptor

Abstract

Conventional dendritic cells (cDCs) are specialized in antigen presentation. In the mouse spleen, cDCs are classified in cDC1s and cDC2s, and express DEC205 and DCIR2 endocytic receptors, respectively. Monoclonal antibodies (mAbs) αDEC205 (αDEC) and αDCIR2 have been fused to different antigens to deliver them to cDC1s or cDC2s. We immunized mice with αDEC and αDCIR2 fused to an antigen using Poly(I:C) as adjuvant. The initial immune response was analyzed from days 3 to 6 after the immunization. We also studied the influence of a booster dose. Our results showed that antigen targeting to cDC1s promoted a pro-inflammatory T H 1 cell response. Antigen targeting to cDC2s induced T FH cells, GCs, and plasma cell differentiation. After boost, antigen targeting to cDC1s improved the T H 1 cell response and induced T H 1-like T FH cells that led to an increase in specific antibody titers and IgG class switch. Additionally, a population of regulatory T cells was also observed. Antigen targeting to cDC2s did not improve the specific antibody response after boost. Our results add new information on the immune response induced after the administration of a booster dose with αDEC and αDCIR2 fusion mAbs. These results may be useful for vaccine design using recombinant mAbs.

Intradermal Delivery of Dendritic Cell-Targeting Chimeric mAbs Genetically Fused to Type 2 Dengue Virus Nonstructural Protein 1

“…Despite that fact, it has become more evident in the literature that the DEC205+ DCs are more prone to induce a Th1 response than the DCIR2+ DCs. On the other hand, DCIR2+ DCs are specialized in the induction of Tfh cells [63,64].…”

STxB as an Antigen Delivery Tool for Mucosal Vaccination

“…Some vectors (STxB, anti-XCR1, adenylate cyclase A) cause TH1 polarization with the production of IgG2a isotype antibodies [ 91 , 99 , 109 ], while others (anti-DEC-205, anti-Dectin 1) result in a mixed TH1/TH17 polarization [ 110 , 111 , 112 ]. Some vectors (anti-Lox-1, anti-Clec9a, anti-DCIR2) appear to be particularly effective in promoting antibody induction, which might be linked to their ability to activate follicular CD4 + T cell [ 103 , 113 , 114 , 115 ]. These mixed humoral and cellular responses provide additional arguments to suggest that the attempt to match the targeting of given types of DC with specific types of immune responses might be an oversimplification.…”

T Cell/B Cell Interactions in the Establishment of Protective Immunity

“…Besides Tfh cells, recent studies have demonstrated that the targeting of antigen-presenting cells is also beneficial. Antigen-fused monoclonal antibodies against DEC205, a surface receptor on a subset of DC, induced Tfh cell differentiation and strong B cell responses in mice [184]. HIV-1vaccinated humanized mice showed enhanced B cell and memory Tfh cell responses after CD40-targeted boost vaccination [185], and targeting of antigen to MHCII molecules in mice significantly increased DC-and B cell-mediated presentation of p:MHCII, resulting in enhanced GC responses [186].…”