Abstract
Two different immune recognition systems have evolved in parallel to recognize peptides starting with an N-formylated methionine, and recognition similarities/differences between these two systems have been investigated. A number of peptides earlier characterized in relation to the H2-M3 complex that presents N-formylated peptides to cytotoxic T cells, have been characterized in relation to the formyl peptide receptors expressed by phagocytic neutrophils in both men (FPRs) and mice (Fprs). FPR1/Fpr1 was identified as the preferred receptor for all fMet-containing peptides examined, but there was no direct correlation between H2-M3 binding and the neutrophil activation potencies. Similarly, there was no direct correlation between the activities induced by the different peptides in human and mouse neutrophils, respectively. The formyl group was important in both H2-M3 binding and FPR activation, but FPR2 was the preferred receptor for the non-formylated peptide. The structural requirements differed between the H2-M3 and FPR/Fpr recognition systems and these data suggest that the two recognition systems have different evolutionary traits.
Highlights
The immune system has developed recognition systems designed to identify microbial/mitochondrial molecular patterns in the form of peptides starting with an N-formylated methionine, the first amino acid incorporated in newly synthesized proteins/peptides in prokaryotes and host cell mitochondria [1, 2]
We have determined the neutrophil activation potency of peptides earlier characterized with respect to M3-binding [19, 22], and the receptor preference for these peptides of murine and human receptors has been determined. We found all these formylated peptides to be very potent activators of neutrophils, but the structural requirements differed between the recognition systems and there were no direct correlations between the reported M3 binding affinity and the neutrophil activating capacity
Formylated peptides are recognized by a group of G-protein coupled chemoattractant receptors, the formyl peptide receptors (FPRs), expressed by phagocytic effector cells that constitute an important part of the innate immune system [5, 7]
Summary
The immune system has developed recognition systems designed to identify microbial/mitochondrial molecular patterns in the form of peptides starting with an N-formylated methionine, the first amino acid incorporated in newly synthesized proteins/peptides in prokaryotes and host cell mitochondria [1, 2]. Microbes and damaged cells/tissues release formylated peptides that are perceived as danger signals and the fMet molecular pattern is recognized by the innate immune system [3, 4]. Neutrophils, the main effector cells in our innate immune defence system express formyl peptide receptors (FPRs) that belong to the 7-transmembrane G protein-coupled receptor (GPCR) family. These receptors regulate innate immmune defense reactions and fine tune inflammatory responses [5,6,7]. The two neutrophil receptors bind structurally diverse agonists, most of which are PLOS ONE | DOI:10.1371/journal.pone.0167529 December 1, 2016
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