Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Vianna, Priscila, Mendes, Marcus F.A., Bragatte, Marcelo A., Ferreira, Priscila S., Salzano, Francisco M., Bonamino, Martin H., Vieira, Gustavo F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952977/
https://www.ncbi.nlm.nih.gov/pubmed/31766602
http://dx.doi.org/10.3390/cells8121488
_version_ 1783486544728817664
author Vianna, Priscila
Mendes, Marcus F.A.
Bragatte, Marcelo A.
Ferreira, Priscila S.
Salzano, Francisco M.
Bonamino, Martin H.
Vieira, Gustavo F.
author_facet Vianna, Priscila
Mendes, Marcus F.A.
Bragatte, Marcelo A.
Ferreira, Priscila S.
Salzano, Francisco M.
Bonamino, Martin H.
Vieira, Gustavo F.
author_sort Vianna, Priscila
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6952977
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-69529772020-01-23 pMHC Structural Comparisons as a Pivotal Element to Detect and Validate T-Cell Targets for Vaccine Development and Immunotherapy—A New Methodological Proposal Vianna, Priscila Mendes, Marcus F.A. Bragatte, Marcelo A. Ferreira, Priscila S. Salzano, Francisco M. Bonamino, Martin H. Vieira, Gustavo F. Cells Hypothesis 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. MDPI 2019-11-22 /pmc/articles/PMC6952977/ /pubmed/31766602 http://dx.doi.org/10.3390/cells8121488 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Hypothesis
Vianna, Priscila
Mendes, Marcus F.A.
Bragatte, Marcelo A.
Ferreira, Priscila S.
Salzano, Francisco M.
Bonamino, Martin H.
Vieira, Gustavo F.
pMHC Structural Comparisons as a Pivotal Element to Detect and Validate T-Cell Targets for Vaccine Development and Immunotherapy—A New Methodological Proposal
title pMHC Structural Comparisons as a Pivotal Element to Detect and Validate T-Cell Targets for Vaccine Development and Immunotherapy—A New Methodological Proposal
title_full pMHC Structural Comparisons as a Pivotal Element to Detect and Validate T-Cell Targets for Vaccine Development and Immunotherapy—A New Methodological Proposal
title_fullStr pMHC Structural Comparisons as a Pivotal Element to Detect and Validate T-Cell Targets for Vaccine Development and Immunotherapy—A New Methodological Proposal
title_full_unstemmed pMHC Structural Comparisons as a Pivotal Element to Detect and Validate T-Cell Targets for Vaccine Development and Immunotherapy—A New Methodological Proposal
title_short pMHC Structural Comparisons as a Pivotal Element to Detect and Validate T-Cell Targets for Vaccine Development and Immunotherapy—A New Methodological Proposal
title_sort pmhc structural comparisons as a pivotal element to detect and validate t-cell targets for vaccine development and immunotherapy—a new methodological proposal
topic Hypothesis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952977/
https://www.ncbi.nlm.nih.gov/pubmed/31766602
http://dx.doi.org/10.3390/cells8121488
work_keys_str_mv AT viannapriscila pmhcstructuralcomparisonsasapivotalelementtodetectandvalidatetcelltargetsforvaccinedevelopmentandimmunotherapyanewmethodologicalproposal
AT mendesmarcusfa pmhcstructuralcomparisonsasapivotalelementtodetectandvalidatetcelltargetsforvaccinedevelopmentandimmunotherapyanewmethodologicalproposal
AT bragattemarceloa pmhcstructuralcomparisonsasapivotalelementtodetectandvalidatetcelltargetsforvaccinedevelopmentandimmunotherapyanewmethodologicalproposal
AT ferreirapriscilas pmhcstructuralcomparisonsasapivotalelementtodetectandvalidatetcelltargetsforvaccinedevelopmentandimmunotherapyanewmethodologicalproposal
AT salzanofranciscom pmhcstructuralcomparisonsasapivotalelementtodetectandvalidatetcelltargetsforvaccinedevelopmentandimmunotherapyanewmethodologicalproposal
AT bonaminomartinh pmhcstructuralcomparisonsasapivotalelementtodetectandvalidatetcelltargetsforvaccinedevelopmentandimmunotherapyanewmethodologicalproposal
AT vieiragustavof pmhcstructuralcomparisonsasapivotalelementtodetectandvalidatetcelltargetsforvaccinedevelopmentandimmunotherapyanewmethodologicalproposal