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Pang, Y.P.* ; Moura, M.C.* ; Thompson, G.E.* ; Nelson, D.R.* ; Hummel, A.M.* ; Jenne, D. ; Emerling, D.* ; Volkmuth, W.* ; Robinson, W.H.* ; Specks, U.*

Remote activation of a latent epitope in an autoantigen decoded with simulated B-factors.

Front. Immunol. 10:2467 (2019)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
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Mutants of a catalytically inactive variant of Proteinase 3 (PR3)-iPR3-Val(103) possessing a Ser195Ala mutation relative to wild-type PR3-Val(103)-offer insights into how autoantigen PR3 interacts with antineutrophil cytoplasmic antibodies (ANCAs) in granulomatosis with polyangiitis (GPA) and whether such interactions can be interrupted. Here we report that iHm5-Val(103), a triple mutant of iPR3-Val(103), bound a monoclonal antibody (moANCA518) from a GPA patient on an epitope remote from the mutation sites, whereas the corresponding epitope of iPR3-Val(103) was latent to moANCA518. Simulated B-factor analysis revealed that the binding of moANCA518 to iHm5-Val(103) was due to increased main-chain flexibility of the latent epitope caused by remote mutations, suggesting rigidification of epitopes with therapeutics to alter pathogenic PR3 center dot ANCA interactions as new GPA treatments.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Autoimmunity ; Autoantigen ; Antigenicity ; Antineutrophil Cytoplasmic Antibody ; Proteinase 3 ; B-factor; Antineutrophil Cytoplasmic Antibodies; Proteinase-3 Pr3; Wegeners-granulomatosis; Neutrophil Elastase; Molecular-dynamics; Capture-elisa; Recognition; Refinement; Interference; Restraints
Language english
Publication Year 2019
HGF-reported in Year 2019
ISSN (print) / ISBN 1664-3224
e-ISSN 1664-3224
Journal Frontiers in Immunology
Quellenangaben Volume: 10, Issue: , Pages: , Article Number: 2467 Supplement: ,
Publisher Frontiers
Publishing Place Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland
Reviewing status Peer reviewed
Institute(s) Institute of Lung Health and Immunity (LHI)
POF-Topic(s) 30202 - Environmental Health
Research field(s) Lung Research
PSP Element(s) G-501600-001
DOI 10.3389/fimmu.2019.02467
WOS ID WOS:000494721700001
Scopus ID 85074569918
PubMed ID 31708920
Erfassungsdatum 2019-11-25
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