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  Multiple-Allele MHC Class II Epitope Engineering by a Molecular Dynamics-Based Evolution Protocol l

Ochoa, R., Lunardelli, V. A. S., Rosa, D. S., Laio, A., & Cossio, P. (2022). Multiple-Allele MHC Class II Epitope Engineering by a Molecular Dynamics-Based Evolution Protocol l. Frontiers in immunology, 13: 862851. doi:10.3389/fimmu.2022.862851.

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 Creators:
Ochoa, Rodrigo1, Author
Lunardelli, Victoria Alves Santos2, Author
Rosa, Daniela Santoro2, 3, Author
Laio, Alessandro4, 5, Author
Cossio, Pilar1, 6, 7, 8, Author           
Affiliations:
1Biophysics of Tropical Diseases, Max Planck Tandem Group, University of Antioquia UdeA, Medellin, Colombia, ou_persistent22              
2Department of Microbiology, Immunology and Parasitology, Federal University of Sao Paulo, Sao Paulo, Brazil, ou_persistent22              
3Institute for Investigation in Immunology (iii), Instituto Nacional de Ciência e Tecnologia (INCT), Sao Paulo, Brazil, ou_persistent22              
4Physics Area, International School for Advanced Studies (SISSA), Trieste, Italy, ou_persistent22              
5Condensed Matter and Statistical Physics Section, International Centre for Theoretical Physics (ICTP), Trieste, Italy, ou_persistent22              
6Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max Planck Society, ou_2068292              
7Center for Computational Mathematics, Flatiron Institute, New York, NY, United States, ou_persistent22              
8Center for Computational Biology, Flatiron Institute, New York, NY, United States, ou_persistent22              

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Free keywords: epitope engineering, MHC class II, molecular dynamics, multiple-allele binding, peptide design
 Abstract: Epitopes that bind simultaneously to all human alleles of Major Histocompatibility Complex class II (MHC II) are considered one of the key factors for the development of improved vaccines and cancer immunotherapies. To engineer MHC II multiple-allele binders, we developed a protocol called PanMHC-PARCE, based on the unsupervised optimization of the epitope sequence by single-point mutations, parallel explicit-solvent molecular dynamics simulations and scoring of the MHC II-epitope complexes. The key idea is accepting mutations that not only improve the affinity but also reduce the affinity gap between the alleles. We applied this methodology to enhance a Plasmodium vivax epitope for multiple-allele binding. In vitro rate-binding assays showed that four engineered peptides were able to bind with improved affinity toward multiple human MHC II alleles. Moreover, we demonstrated that mice immunized with the peptides exhibited interferon-gamma cellular immune response. Overall, the method enables the engineering of peptides with improved binding properties that can be used for the generation of new immunotherapies.

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Language(s): eng - English
 Dates: 2022-01-262022-03-282022-04-27
 Publication Status: Published online
 Pages: 14
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.3389/fimmu.2022.862851
BibTex Citekey: ochoa_multiple-allele_2022
 Degree: -

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Title: Frontiers in immunology
  Abbreviation : Front immunol
Source Genre: Journal
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Publ. Info: Lausanne : Frontiers Media
Pages: - Volume / Issue: 13 Sequence Number: 862851 Start / End Page: - Identifier: ISSN: 1664-3224
CoNE: https://pure.mpg.de/cone/journals/resource/1664-3224