Identification of B cell epitopes enhanced by protein unfolding and aggregation.
Aggregation
B cell epitope
Biopharmaceutical
Immunogenicity
Journal
Molecular immunology
ISSN: 1872-9142
Titre abrégé: Mol Immunol
Pays: England
ID NLM: 7905289
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
26
07
2018
revised:
16
10
2018
accepted:
30
11
2018
pubmed:
15
12
2018
medline:
1
5
2019
entrez:
15
12
2018
Statut:
ppublish
Résumé
Aggregation of therapeutic proteins is a key factor in the generation of unwanted immunogenicity, and can result in reduced serum half-life, neutralization of function and adverse health effects. There is currently little information regarding how aggregates interact with B-cell receptors or cognate antibodies at the protein sequence level, or whether non-native, aggregate-induced epitopes predominate in these interactions. Using an antibody fragment (single chain antibody variable fragment; scFv) that forms aggregates readily at low temperature, anti-scFv IgG antibody responses were generated by intraperitoneal injection of BALB/c strain mice with monomer or aggregate preparations. Aggregate-specific immunosignatures were identified by oligo-peptide microarray fine epitope mapping, using overlapping 15mer peptides based on the linear sequence of scFv, printed onto glass slides. IgG antibodies from mice immunized with aggregated scFv preferentially recognized a patch of overlapping peptides. This region mapped to a β-strand located at the interface between the V
Identifiants
pubmed: 30550980
pii: S0161-5890(18)30518-2
doi: 10.1016/j.molimm.2018.11.020
pmc: PMC6344229
pii:
doi:
Substances chimiques
Epitopes, B-Lymphocyte
0
Immunoglobulin G
0
Protein Aggregates
0
Single-Chain Antibodies
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
181-189Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 105610/Z/14/Z
Pays : United Kingdom
Informations de copyright
Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.
Références
J Pharm Sci. 2016 Feb;105(2):417-430
pubmed: 26869409
Rejuvenation Res. 2014 Apr;17(2):97-104
pubmed: 24164623
Immunology. 2017 Mar;150(3):343-355
pubmed: 27859059
PLoS One. 2014 Jan 21;9(1):e86322
pubmed: 24466023
J Immunol Methods. 1992 Jun 24;150(1-2):77-90
pubmed: 1613260
Immunology. 2017 Nov;152(3):425-438
pubmed: 28640942
AAPS J. 2006 Aug 04;8(3):E501-7
pubmed: 17025268
PLoS One. 2015 Mar 27;10(3):e0121673
pubmed: 25816293
J Biol Chem. 2007 Jan 26;282(4):2229-36
pubmed: 17135263
Eur J Pharm Biopharm. 2017 Jun;115:18-30
pubmed: 28161552
J Transl Med. 2015 Oct 29;13:339
pubmed: 26511203
Nat Commun. 2014 Sep 03;5:4785
pubmed: 25183057
Microb Cell Fact. 2015 Apr 16;14:57
pubmed: 25890161
Pharm Res. 2015 Apr;32(4):1383-94
pubmed: 25319104
MAbs. 2015;7(4):662-71
pubmed: 25962087
Theranostics. 2017 Oct 17;7(19):4699-4709
pubmed: 29187897
Proteins. 2011 Sep;79(9):2637-47
pubmed: 21732420
Mol Pharm. 2017 Apr 3;14(4):1292-1299
pubmed: 28206769
Biopolymers. 2000;55(3):188-206
pubmed: 11074414
J Chem Theory Comput. 2015 Aug 11;11(8):3696-713
pubmed: 26574453
Immunology. 2014 Aug;142(4):526-35
pubmed: 24635566
MAbs. 2015;7(3):525-39
pubmed: 25875351
J Biol Chem. 2012 Jul 20;287(30):25266-79
pubmed: 22584577
Nature. 2016 Aug 31;537(7618):50-6
pubmed: 27582220
Pharm Res. 2011 May;28(5):949-61
pubmed: 21437790
Biotechnol Bioeng. 2010 Jun 15;106(3):367-75
pubmed: 20178123
Nat Methods. 2015 Jan;12(1):7-8
pubmed: 25549265
J Pharm Sci. 2009 Sep;98(9):2909-34
pubmed: 18823031
Annu Rev Chem Biomol Eng. 2012;3:263-86
pubmed: 22468604
Proc Natl Acad Sci U S A. 2013 Nov 12;110(46):18614-9
pubmed: 24167296
J Immunotoxicol. 2014 Apr-Jun;11(2):99-109
pubmed: 23919460
Trends Pharmacol Sci. 2010 Feb;31(2):53-9
pubmed: 19963283
J Biol Chem. 2011 Jul 15;286(28):25118-33
pubmed: 21454532
Cell Immunol. 2015 Jun;295(2):118-26
pubmed: 25880103
Pharm Res. 2015 Jul;32(7):2344-59
pubmed: 25630815
Nat Rev Immunol. 2010 May;10(5):301-16
pubmed: 20414204
Nat Rev Rheumatol. 2013 Mar;9(3):164-72
pubmed: 23399692
Oncologist. 2016 Oct;21(10):1260-1268
pubmed: 27440064
Toxicol Sci. 2016 Oct;153(2):258-70
pubmed: 27370416
Mol Divers. 2004;8(3):291-9
pubmed: 15384422