title: The Novel Toll-Like Receptor 2 Agonist SUP3 Enhances Antigen Presentation and T Cell Activation by Dendritic Cells.
abstract: Dendritic cells (DCs) are highly specialized antigen-presenting cells that play crucial roles in innate and adaptive immunity. Previous studies suggested that Toll-like receptor (TLR) agonists could be used as potential adjuvants, as activation of TLRs can boost DC-induced immune responses. TLR2 agonists have been shown to enhance DC-mediated immune responses. However, classical TLR2 agonists such as Pam3CSK4 are not stable enoughin vivo, which limits their clinical applications. In this study, a novel structurally stable TLR2 agonist named SUP3 was designed. Functional analysis showed that SUP3 induced much stronger antitumor response than Pam3CSK4 by promoting cytotoxic T lymphocytes activationin vivo. This effect was achieved through the following mechanisms: SUP3 strongly enhanced the ability of antigen cross-presentation by DCs and subsequent T cell activation. SUP3 upregulated the expression of costimulatory molecules on DCs and increased antigen deposition in draining lymph nodes. More interestingly, SUP3 induced less amount of pro-inflammatory cytokine productionin vivocompared to other TLR agonists such as lipopolysaccharide. Taken together, SUP3 could serve as a novel promising immune adjuvant in vaccine development and immune modulations.
authors.affiliation: Institute for Immunology, Tsinghua-Peking Center for Life Sciences, Tsinghua University School of Medicine , Beijing , China.
authors.forename: Xueheng
authors.initials: X
authors.lastname: Guo
authors.affiliation: Institute for Immunology, Tsinghua-Peking Center for Life Sciences, Tsinghua University School of Medicine , Beijing , China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wu
authors.affiliation: Institute for Immunology, Tsinghua-Peking Center for Life Sciences, Tsinghua University School of Medicine, Beijing, China; College of Veterinary Medicine, Shandong Agricultural University, Tai'an, Shandong, China.
authors.forename: Yingli
authors.initials: Y
authors.lastname: Shang
authors.affiliation: Institute for Immunology, Tsinghua-Peking Center for Life Sciences, Tsinghua University School of Medicine , Beijing , China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Institute for Immunology, Tsinghua-Peking Center for Life Sciences, Tsinghua University School of Medicine , Beijing , China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.affiliation: Institute for Immunology, Tsinghua-Peking Center for Life Sciences, Tsinghua University School of Medicine , Beijing , China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University School of Pharmaceutical Sciences , Beijing , China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Institute for Immunology, Tsinghua-Peking Center for Life Sciences, Tsinghua University School of Medicine , Beijing , China.
authors.forename: Jiaoyan
authors.initials: J
authors.lastname: Huang
authors.affiliation: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University School of Pharmaceutical Sciences , Beijing , China.
authors.forename: Xuebin
authors.initials: X
authors.lastname: Liao
authors.affiliation: Institute for Immunology, Tsinghua-Peking Center for Life Sciences, Tsinghua University School of Medicine , Beijing , China.
authors.forename: Li
authors.initials: L
authors.lastname: Wu
keywords: TLR2 agonist; adjuvant; antigen presentation; cytotoxic T lymphocyte; dendritic cell