N-Terminal Peptide of PGLYRP1/Tag7 Is a Novel Ligand for TREM-1 Receptor

Abstract

An investigation of innate immunity receptors sheds light on the mechanisms of inflammation and associated immune reactions. One of the key immune regulators is the TREM-1 receptor, which is involved in both inflammation and antitumor immune response. In this article, we have obtained a new ligand for the TREM-1 receptor. The peptide, named N3, is a part of the innate immune protein PGLYRP1/Tag7. It is responsible for activating the TREM-1 signaling pathway. Here, we have demonstrated that the N3 peptide acts like other TREM-1 receptor ligands: its binding results in a mild inflammation response and appearance of cytotoxic lymphocytes. We have shown that cytotoxic populations of lymphocytes in N3 peptide-treated PBMCs are similar to those treated with Tag7 or Hsp70. We also determined the part of the N3 peptide responsible for binding to TREM-1. The resulting peptide (N9) consists of nine amino acids and can be considered as a potential peptide that blocks TREM-1 signaling.

The biology of TREM receptors

“…Despite considerable progress in the functional characterization of triggering receptor expressed on myeloid cells 1 (TREM1), TREM1 ligands remain incompletely defined. Two studies have implicated peptidoglycan recognition protein 1 as a ligand for TREM1, either as a complex with bacterially derived peptidoglycan 220 or as an N-terminal peptide 221 . Another study has shown that TREM1 binds to the extracellular cold-inducible RNA-binding protein eCIRP, an endogenous molecule that can be released by damaged tissues 222 .…”

The Interaction of HMGB1 with the Proinflammatory TREM-1 Receptor Generates Cytotoxic Lymphocytes Active against HLA-Negative Tumor Cells

“…Previously, we investigated the effect of IL-2 on the activation of cytotoxic lymphocytes and for the first time showed that CD4+ and CD8+ cytotoxic T lymphocytes are generated under the action of this cytokine, killing HLA-negative tumor cells via FasL-Fas interaction [ 30 , 31 ].…”

“…Pierce™ Chromogenic Endotoxin Quant Kit (Thermo Fisher Scientific, Rockford, Illinois, USA) was used to confirm absence of LPS in recombinant protein. Tag7 was obtained as described [ 31 ], sTREM-1 was obtained according to [ 30 ]. The BSA was from Sigma (Sigma–Aldrich, St. Louis, MI, USA).…”