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

Author:
Sun, Weilai, Li, Qiao, Ning, Xiuzhe, Yang, Yi, Guo, Jingjing, Zhu, Qing, Guo, Yan, Li, Hao, Wang, Yuepeng, Zhou, Yusen, Kou, Zhihua
Source:
Vaccine 2020 v.38 no.2 pp. 288-297
ISSN:
0264-410X
Subject:
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
Abstract:
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.
Agid:
6721880