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Identification of CD4(+) T cell epitopes from Staphylococcus aureus secretome using immunoinformatic prediction and molecular docking

One major reason for the lack of clinical success of Staphylococcus aureus vaccine candidates is the inability of the antigens to develop a CD4(+) T cell-mediated immune response. Hence, it is important to identify CD4(+) T cell antigens from S. aureus. CD4(+) T cells are activated following the pre...

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Autores principales: Francis, Dileep, Kumar, Arun, Chittalakkottu, Sadasivan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Termedia Publishing House 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9642919/
https://www.ncbi.nlm.nih.gov/pubmed/36605712
http://dx.doi.org/10.5114/bta.2021.103761
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author Francis, Dileep
Kumar, Arun
Chittalakkottu, Sadasivan
author_facet Francis, Dileep
Kumar, Arun
Chittalakkottu, Sadasivan
author_sort Francis, Dileep
collection PubMed
description One major reason for the lack of clinical success of Staphylococcus aureus vaccine candidates is the inability of the antigens to develop a CD4(+) T cell-mediated immune response. Hence, it is important to identify CD4(+) T cell antigens from S. aureus. CD4(+) T cells are activated following the presentation of epitopes derived from exogenous proteins on HLA class II molecules. Fifty-nine secretory proteins of S. aureus were analyzed computationally for the presence of HLA class II binding peptides. Fifteen-mer peptides were generated, and their binding to 26 HLA class II alleles was predicted. The structural feasibility of the peptides binding to HLA-II was studied using molecular docking. Of the 16,724 peptides generated, 6991 (41.8%) were predicted to bind to any one of the alleles with an IC(50) value below 50 nM. Comparative sequence analysis revealed that only 545 of the strong binding peptides are non-self in the human system. Approximately 50% of the binding peptides were monoallele-specific. Moreover, approximately 95% of the predicted strong binding non-self peptides interacted with the binding groove of at least one HLA class II molecule with a glide score better than –10 kcal/mol. On the basis of the analysis of the strength of binding, non-self presentation in the human host, propensity to bind to a higher number of alleles, and energetically favorable interactions with HLA molecules, a set of 11 CD4(+) T cell epitopes that can be used as vaccine candidates was identified.
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spelling pubmed-96429192023-01-04 Identification of CD4(+) T cell epitopes from Staphylococcus aureus secretome using immunoinformatic prediction and molecular docking Francis, Dileep Kumar, Arun Chittalakkottu, Sadasivan BioTechnologia (Pozn) Research Papers One major reason for the lack of clinical success of Staphylococcus aureus vaccine candidates is the inability of the antigens to develop a CD4(+) T cell-mediated immune response. Hence, it is important to identify CD4(+) T cell antigens from S. aureus. CD4(+) T cells are activated following the presentation of epitopes derived from exogenous proteins on HLA class II molecules. Fifty-nine secretory proteins of S. aureus were analyzed computationally for the presence of HLA class II binding peptides. Fifteen-mer peptides were generated, and their binding to 26 HLA class II alleles was predicted. The structural feasibility of the peptides binding to HLA-II was studied using molecular docking. Of the 16,724 peptides generated, 6991 (41.8%) were predicted to bind to any one of the alleles with an IC(50) value below 50 nM. Comparative sequence analysis revealed that only 545 of the strong binding peptides are non-self in the human system. Approximately 50% of the binding peptides were monoallele-specific. Moreover, approximately 95% of the predicted strong binding non-self peptides interacted with the binding groove of at least one HLA class II molecule with a glide score better than –10 kcal/mol. On the basis of the analysis of the strength of binding, non-self presentation in the human host, propensity to bind to a higher number of alleles, and energetically favorable interactions with HLA molecules, a set of 11 CD4(+) T cell epitopes that can be used as vaccine candidates was identified. Termedia Publishing House 2021-03-31 /pmc/articles/PMC9642919/ /pubmed/36605712 http://dx.doi.org/10.5114/bta.2021.103761 Text en © 2021 Institute of Bioorganic Chemistry, Polish Academy of Sciences https://creativecommons.org/licenses/by-nc-nd/3.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs (CC BY-NC-ND), allowing third parties to download and share its works but not commercially purposes or to create derivative works.
spellingShingle Research Papers
Francis, Dileep
Kumar, Arun
Chittalakkottu, Sadasivan
Identification of CD4(+) T cell epitopes from Staphylococcus aureus secretome using immunoinformatic prediction and molecular docking
title Identification of CD4(+) T cell epitopes from Staphylococcus aureus secretome using immunoinformatic prediction and molecular docking
title_full Identification of CD4(+) T cell epitopes from Staphylococcus aureus secretome using immunoinformatic prediction and molecular docking
title_fullStr Identification of CD4(+) T cell epitopes from Staphylococcus aureus secretome using immunoinformatic prediction and molecular docking
title_full_unstemmed Identification of CD4(+) T cell epitopes from Staphylococcus aureus secretome using immunoinformatic prediction and molecular docking
title_short Identification of CD4(+) T cell epitopes from Staphylococcus aureus secretome using immunoinformatic prediction and molecular docking
title_sort identification of cd4(+) t cell epitopes from staphylococcus aureus secretome using immunoinformatic prediction and molecular docking
topic Research Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9642919/
https://www.ncbi.nlm.nih.gov/pubmed/36605712
http://dx.doi.org/10.5114/bta.2021.103761
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