Affiliation:
1. Biomedical Innovations Research for Translational Health Science (BIRTHS) Laboratory, Department of Biochemistry and Molecular Biology, College of Medicine, University of the Philippines Manila, Manila, Philippines
Abstract
Background:
B-cell epitope prediction is a computational approach originally developed
to support the design of peptide-based vaccines for inducing protective antibody-mediated immunity,
as exemplified by neutralization of biological activity (e.g., pathogen infectivity). Said approach
is benchmarked against experimentally obtained data on paratope-epitope binding; but such
data are curated primarily on the basis of immune-complex structure, obscuring the role of antigen
conformational disorder in the underlying immune recognition process.
Objective:
This work aimed to critically analyze the curation of epitope-paratope binding data that
are relevant to B-cell epitope prediction for peptide-based vaccine design.
Methods:
Database records on neutralizing monoclonal antipeptide antibody immune-complex
structure were retrieved from the Immune Epitope Database (IEDB) and analyzed in relation to
other data from both IEDB and external sources including the Protein Data Bank (PDB) and published
literature, with special attention to data on conformational disorder among paratope-bound
and unbound peptidic antigens.
Results:
Data analysis revealed key examples of antipeptide antibodies that recognize conformationally disordered B-cell epitopes and thereby neutralize the biological activity of cognate targets (e.g., proteins and pathogens), with inconsistency noted in the mapping of some epitopes due to reliance on immune-complex structural details, which vary even among experiments utilizing the same paratope-epitope combination (e.g., with the epitope forming part of a peptide or a protein).
Conclusion:
The results suggest an alternative approach to curating paratope-epitope binding data based on neutralization of biological activity by polyclonal antipeptide antibodies, with reference to immunogenic peptide sequences and their conformational disorder in unbound antigen structures.
Funder
University of the Philippines System
Publisher
Bentham Science Publishers Ltd.
Subject
Biochemistry,General Medicine,Structural Biology
Cited by
3 articles.
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