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A High Throughput MHC II Binding Assay for Quantitative Analysis of Peptide Epitopes
Published on: March 25, 2014
Prediction of Variable-Length B-Cell Epitopes for Antipeptide Paratopes Using the Program HAPTIC
1Biomedical Innovations Research for Translational Health Science (BIRTHS) Laboratory, Department of Biochemistry and Molecular Biology, College of Medicine, University of the Philippines Manila, Manila, Philippines.
Background:
B-cell epitope prediction for antipeptide antibody responses enables peptide-based vaccine design and related translational applications. This entails estimating epitopeparatope binding free-energy changes from antigen sequence; but attempts to do so assuming uniform epitope length (e.g., of hexapeptide sequences, each spanning a typical paratope diameter when fully extended) have neglected empirically established variation in epitope length.
Objective:
This work aimed to develop a sequence-based physicochemical approach to variablelength B-cell epitope prediction for antipeptide paratopes recognizing flexibly disordered targets.
Methods:
Said approach was developed by analogy between epitope-paratope binding and protein folding modeled as polymer collapse, treating paratope structure implicitly. Epitope-paratope binding was thus conceptually resolved into processes of epitope compaction, collapse and contact, with epitope collapse presenting the main entropic barrier limiting epitope length among nonpolyproline sequences. The resulting algorithm was implemented as a computer program, namely the Heuristic Affinity Prediction Tool for Immune Complexes (HAPTIC), which is freely accessible via an online interface (http://badong.freeshell.org/haptic.htm). This was used in conjunction with published data on representative known peptide immunogens.
Results:
HAPTIC predicted immunodominant epitope sequences with lengths limited by penalties for both compaction and collapse, consistent with known paratope-bound structures of flexibly disordered epitopes. In most cases, the predicted association constant was greater than its experimentally determined counterpart but below the predicted upper bound for affinity maturation in vivo.
Conclusion:
HAPTIC provides a physicochemically plausible means for estimating the affinity of antipeptide paratopes for sterically accessible and flexibly disordered peptidic antigen sequences by explicitly considering candidate B-cell epitopes of variable length.
