Glucopeptides derived from myelin‐relevant proteins and hyperglucosylated nontypeable Haemophilus influenzae bacterial adhesin cross‐react with multiple sclerosis specific antibodies: A step forward in the identification of native autoantigens in multiple sclerosis

Abstract

Multiple sclerosis (MS) is an inflammatory and autoimmune disorder, in which an antibody‐mediated demyelination mechanism plays a critical role. We prepared two glucosylated peptides derived from the human myelin proteins, that is, oligodendrocyte‐myelin glycoprotein (OMGp) and reticulon‐4 receptor (RTN4R), selected by a bioinformatic approach for their conformational homology with CSF114(Glc), a designed β‐turn antigenic probe derived from myelin oligodendrocyte glycoprotein (MOG), a glycoprotein present in the CNS. This synthetic antigen is specifically recognized by antibodies in sera of MS patients. We report herein the antigenic properties of these peptides, showing, on the one hand, that MS patient antibodies recognize the two glucosylated peptides and, on the other hand, that these antibodies cross‐react with CSF114(Glc) and with the previously described hyperglucosylated nontypeable Haemophilus influenzae bacterial adhesin protein HMW1ct(Glc). These observations point to an immunological association between human and bacterial protein antigens, underpinning the hypothesis that molecular mimicry triggers the breakdown of self‐tolerance in MS and suggesting that RTN4R and OMGp can be considered as autoantigens.

Antiviral Activity against SARS-CoV-2 of Conformationally Constrained Helical Peptides Derived from Angiotensin-Converting Enzyme 2

“…The peptides were synthesized using the Liberty Blue automated microwave peptide synthesizer (CEM Corporation, Matthews, NC, USA) following the Fmoc/tBu strategy and using Tentagel S RAM resin (loading 0.23 mmol/g) as previously described. 52 The following Fmoc-amino acids were used: Fmoc-Ala-OH, Fmoc-Asp(tBu)-OH, Fmoc-Glu(tBu)-OH, Fmoc-Phe-OH, Fmoc-His(Trt)-OH, Fmoc-Lys(Boc)-OH, Fmoc-Leu-OH, Fmoc-Asn(Trt)-OH, Fmoc-Gln(Trt), Fmoc-Thr(tBu)-OH, Fmoc-Tyr(tBu)-OH, Fmoc-Nle(ε-N 3 )-OH, and Fmoc-Pra-OH. The Fmoc deprotections were performed using a solution of 20% piperidine in DMF (2 M).…”

Competitive ELISA for the identification of 35–55 myelin oligodendrocyte glycoprotein immunodominant epitope conjugated with mannan

“…Multiple sclerosis (MS) is an immunologically controlled, inflammatory disease of the central nervous system (CNS) characterized by myelin damage 1,2 . Moreover, MS patient antibodies recognize glucopeptides derived from human myelin proteins 3 . Many studies have shown that myelin oligodendrocyte glycoprotein (MOG) is an important autoantigen that is associated with MS and experimental autoimmune encephalomyelitis (EAE: an animal model for T cell‐mediated inflammatory and demyelinating diseases) 4,5 .…”