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Open AccessHypothesis

pMHC Structural Comparisons as a Pivotal Element to Detect and Validate T-Cell Targets for Vaccine Development and Immunotherapy—A New Methodological Proposal

1
Laboratory of Human Teratogenesis and Population Medical Genetics, Department of Genetics, Institute of Biosciences, Federal University of Rio Grande do Sul, Porto Alegre 91.501-970, Brazil
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Laboratory of Bioinformatics (NBLI), Department of Genetics, Institute of Biosciences, Federal University of Rio Grande do Sul, Porto Alegre 91.501-970, Brazil
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Program of Immunology and Tumor Biology, Division of Experimental and Translational Research, Brazilian National Cancer Institute, Rio de Janeiro 20231-050, Brazil
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Laboratory of Molecular Evolution, Department of Genetics, Institute of Biosciences, Federal University of Rio Grande do Sul, Porto Alegre 91.501-970, Brazil
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Vice Presidency of Research and Biological Collections, Fundação Oswaldo Cruz, Rio de Janeiro 21040-900, Brazil
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Laboratory of Health Bioinformatics, Post Graduate Program in Health and Human Development, La Salle University, Canoas 91.501-970, Brazil
*
Author to whom correspondence should be addressed.
Cells 2019, 8(12), 1488; https://doi.org/10.3390/cells8121488
Received: 26 September 2019 / Revised: 15 November 2019 / Accepted: 16 November 2019 / Published: 22 November 2019
(This article belongs to the Section Cellular Immunology)
The search for epitopes that will effectively trigger an immune response remains the “El Dorado” for immunologists. The development of promising immunotherapeutic approaches requires the appropriate targets to elicit a proper immune response. Considering the high degree of HLA/TCR diversity, as well as the heterogeneity of viral and tumor proteins, this number will invariably be higher than ideal to test. It is known that the recognition of a peptide-MHC (pMHC) by the T-cell receptor is performed entirely in a structural fashion, where the atomic interactions of both structures, pMHC and TCR, dictate the fate of the process. However, epitopes with a similar composition of amino acids can produce dissimilar surfaces. Conversely, sequences with no conspicuous similarities can exhibit similar TCR interaction surfaces. In the last decade, our group developed a database and in silico structural methods to extract molecular fingerprints that trigger T-cell immune responses, mainly referring to physicochemical similarities, which could explain the immunogenic differences presented by different pMHC-I complexes. Here, we propose an immunoinformatic approach that considers a structural level of information, combined with an experimental technology that simulates the presentation of epitopes for a T cell, to improve vaccine production and immunotherapy efficacy. View Full-Text
Keywords: viral epitopes; cellular immunology; cancer targets discovery; immunotherapy targets viral epitopes; cellular immunology; cancer targets discovery; immunotherapy targets
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MDPI and ACS Style

Vianna, P.; Mendes, M.F.; Bragatte, M.A.; Ferreira, P.S.; Salzano, F.M.; Bonamino, M.H.; Vieira, G.F. pMHC Structural Comparisons as a Pivotal Element to Detect and Validate T-Cell Targets for Vaccine Development and Immunotherapy—A New Methodological Proposal. Cells 2019, 8, 1488.

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