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2017 ; 8
(ä): 158
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The Novel Toll-Like Receptor 2 Agonist SUP3 Enhances Antigen Presentation and T
Cell Activation by Dendritic Cells
#MMPMID28270814
Guo X
; Wu N
; Shang Y
; Liu X
; Wu T
; Zhou Y
; Liu X
; Huang J
; Liao X
; Wu L
Front Immunol
2017[]; 8
(ä): 158
PMID28270814
show ga
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 enough in 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 activation
in 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 production in vivo compared to
other TLR agonists such as lipopolysaccharide. Taken together, SUP3 could serve
as a novel promising immune adjuvant in vaccine development and immune
modulations.