Main content area

TFPR1 acts as an immune regulator and an efficient adjuvant for proteins and peptides by activating immune cells, primarily through TLR2

Sun, Weilai, Li, Qiao, Ning, Xiuzhe, Yang, Yi, Guo, Jingjing, Zhu, Qing, Guo, Yan, Li, Hao, Wang, Yuepeng, Zhou, Yusen, Kou, Zhihua
Vaccine 2020 v.38 no.2 pp. 288-297
B-lymphocytes, Escherichia coli, Human immunodeficiency virus 1, Toll-like receptor 2, adjuvants, animal models, antibodies, cell-mediated immunity, cytokines, hepatitis B antigens, immunomodulation, immunomodulators, macrophages, reverse transcriptase polymerase chain reaction, secretion, snakes, splenocytes, vaccines, viper venoms
Triflin, a non-toxic protein found in the venom of the Habu snake, belongs to the CRISP (cysteine-rich secretory protein) family, which comprises two domains: a C-terminal cysteine-rich domain (CRD) and an N-terminal pathogenesis-related-1 (PR-1) domain. The function of the highly structurally conserved PR-1 domain is unknown. Here, we successfully expressed the PR-1 domain of triflin (hereafter called TFPR1) in E. coli. Animal experiments showed that TFPR1 augmented Th1-biased antibody- and cell-mediated immune responses in mice immunized with two protein antigens (OVA and HBsAg) or a peptide antigen (HIV-1 pep). A flow cytometry-based binding assay and in vitro stimulation with TFPR1 showed that it triggered Th1-biased proinflammatory and immunoregulatory cytokine secretion primarily by binding to B cells and macrophages within the mouse splenocyte population. Quantitative RT-PCR, antibody blocking assays using a specific anti-mTLR2 antibody, and stimulatory experiments in vitro using splenocytes from TLR2-KO mice demonstrated that TFPR1 activated murine immune cells, primarily by stimulating toll-like receptor 2 (TLR2). These results suggest that TFPR1 acts as a novel immune modulator and potent adjuvant primarily by activating TLR2. Thus, the PR-1-based core domain might play a role in immune regulation.