Targeting Conventional Dendritic Cells to Fine-Tune Antibody Responses

Abstract

Dendritic cells (DCs) facilitate cross talk between the innate and adaptive immune system. They sense and phagocytose invading pathogens, and are not only capable of activating naïve T cells, but can also determine the polarization of T cell responses into different effector subtypes. Polarized T cells in turn have a crucial role in antibody class switching and affinity maturation, and consequently the quality of the resulting humoral immunity. Targeting vaccines to DCs thus provides a great deal of opportunities for influencing the humoral immune responses, by fine-tuning the T cell response as well as regulating antigen availability for B cells. In this review we aim to outline how different DC targeted vaccination strategies can be utilized to induce a desired humoral immune response. A range of factors, including route of vaccine administration, use of adjuvants, choice of DC subset and surface receptor to target have been reported to influence the resulting immune response and will be reviewed herein. Finally, we will discuss opportunities for designing improved vaccines and challenges with translating this knowledge into clinical or veterinary medicine.

Keywords: DC subtypes; Th1 & Th2; antibody; dendritic cell (DC); targeting; vaccination.

Figure 1

Targeting DC subsets to influence the polarization of the antibody response. (A) Targeting the receptors Xcr1, Clec9a and DEC-205 can be used to deliver antigen to cDC1s, while targeting DCIR2 and TLR5 will deliver antigen to cDC2s. Targeting CD11c will deliver antigen to both DC subsets. (B) Delivery of antigen to cDC1s or cDC2s will result in presentation of antigen derived peptides on MHC-II. Secretion of cytokines such as IL-12 by cDC1s, or IL10 and IL33 by cDC2s, can initiate polarization of the T helper cell responses in direction of Th1 or Th2, respectively. In addition, both cDC1s and cDC2s have been reported to induce T_FH cells, although cDC2s are likely more important in this respect. (C) T_FH cells migrate to germinal center where they regulate isotype switching of antigen specific B cells through secretion of IFNγ (IgG2a) or IL4 (IgG1). Th1 may also contribute to isotype switching through secretion of IFNγ, while it is less clear if Th2 cells contribute to IgG1 switching by secretion of IL4. T_FH cells further regulate affinity maturation of the antigen specific B cells, and secrete IL-21 resulting in the formation of plasma cells and secretion of high affinity antibodies.