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

Eur J Immunol. 2020 Dec;50(12):1895-1911. doi: 10.1002/eji.202048694. Epub 2020 Jul 26.

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 TH 1 cell response. Antigen targeting to cDC2s induced TFH cells, GCs, and plasma cell differentiation. After boost, antigen targeting to cDC1s improved the TH 1 cell response and induced TH 1-like TFH 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.

Keywords: DCIR2; DEC205; antigen targeting; dendritic cells; monoclonal antibodies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibody Formation / immunology
  • Antigen Presentation / immunology
  • Dendritic Cells / immunology*
  • Female
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Poly I-C / immunology
  • Receptors, Cell Surface / immunology*
  • T Follicular Helper Cells / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Th1 Cells / immunology*

Substances

  • Antibodies, Monoclonal
  • Receptors, Cell Surface
  • Poly I-C