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Correlative CD4 and CD8 T-cell immunodominance in humans and mice: Implications for preclinical testing

Antigen-specific T-cell recognition is restricted by Major Histocompatibility Complex (MHC) molecules, and differences between CD4 and CD8 immunogenicity in humans and animal species used in preclinical vaccine testing are yet to be fully understood. In this study, we addressed this matter by analyz...

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Autores principales: Neto, Tertuliano Alves Pereira, Sidney, John, Grifoni, Alba, Sette, Alessandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616275/
https://www.ncbi.nlm.nih.gov/pubmed/37726420
http://dx.doi.org/10.1038/s41423-023-01083-0
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author Neto, Tertuliano Alves Pereira
Sidney, John
Grifoni, Alba
Sette, Alessandro
author_facet Neto, Tertuliano Alves Pereira
Sidney, John
Grifoni, Alba
Sette, Alessandro
author_sort Neto, Tertuliano Alves Pereira
collection PubMed
description Antigen-specific T-cell recognition is restricted by Major Histocompatibility Complex (MHC) molecules, and differences between CD4 and CD8 immunogenicity in humans and animal species used in preclinical vaccine testing are yet to be fully understood. In this study, we addressed this matter by analyzing experimentally identified epitopes based on published data curated in the Immune Epitopes DataBase (IEDB) database. We first analyzed SARS-CoV-2 spike (S) and nucleoprotein (N), which are two common targets of the immune response and well studied in both human and mouse systems. We observed a weak but statistically significant correlation between human and H-2(b) mouse T-cell responses (CD8 S specific (r = 0.206, p = 1.37 × 10(−13)); CD4 S specific (r = 0.118, p = 2.63 × 10(−5)) and N specific (r = 0.179, p = 2.55 × 10(−4))). Due to intrinsic differences in MHC molecules across species, we also investigated the association between the immunodominance of common Human Leukocyte Antigen (HLA) alleles for which HLA transgenic mice are available, namely, A*02:01, B*07:02, DRB1*01:01, and DRB1*04:01, and found higher significant correlations for both CD8 and CD4 (maximum r = 0.702, p = 1.36 × 10(−31) and r = 0.594, p = 3.04(−122), respectively). Our results further indicated that some regions are commonly immunogenic between humans and mice (either H-2(b) or HLA transgenic) but that others are human specific. Finally, we noted a significant correlation between CD8 and CD4 S- (r = 0.258, p = 7.33 × 10(21)) and N-specific (r = 0.369, p = 2.43 × 10(14)) responses, suggesting that discrete protein subregions can be simultaneously recognized by T cells. These findings were confirmed in other viral systems, providing general guidance for the use of murine models to test T-cell immunogenicity of viral antigens destined for human use.
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spelling pubmed-106162752023-11-14 Correlative CD4 and CD8 T-cell immunodominance in humans and mice: Implications for preclinical testing Neto, Tertuliano Alves Pereira Sidney, John Grifoni, Alba Sette, Alessandro Cell Mol Immunol Article Antigen-specific T-cell recognition is restricted by Major Histocompatibility Complex (MHC) molecules, and differences between CD4 and CD8 immunogenicity in humans and animal species used in preclinical vaccine testing are yet to be fully understood. In this study, we addressed this matter by analyzing experimentally identified epitopes based on published data curated in the Immune Epitopes DataBase (IEDB) database. We first analyzed SARS-CoV-2 spike (S) and nucleoprotein (N), which are two common targets of the immune response and well studied in both human and mouse systems. We observed a weak but statistically significant correlation between human and H-2(b) mouse T-cell responses (CD8 S specific (r = 0.206, p = 1.37 × 10(−13)); CD4 S specific (r = 0.118, p = 2.63 × 10(−5)) and N specific (r = 0.179, p = 2.55 × 10(−4))). Due to intrinsic differences in MHC molecules across species, we also investigated the association between the immunodominance of common Human Leukocyte Antigen (HLA) alleles for which HLA transgenic mice are available, namely, A*02:01, B*07:02, DRB1*01:01, and DRB1*04:01, and found higher significant correlations for both CD8 and CD4 (maximum r = 0.702, p = 1.36 × 10(−31) and r = 0.594, p = 3.04(−122), respectively). Our results further indicated that some regions are commonly immunogenic between humans and mice (either H-2(b) or HLA transgenic) but that others are human specific. Finally, we noted a significant correlation between CD8 and CD4 S- (r = 0.258, p = 7.33 × 10(21)) and N-specific (r = 0.369, p = 2.43 × 10(14)) responses, suggesting that discrete protein subregions can be simultaneously recognized by T cells. These findings were confirmed in other viral systems, providing general guidance for the use of murine models to test T-cell immunogenicity of viral antigens destined for human use. Nature Publishing Group UK 2023-09-19 2023-11 /pmc/articles/PMC10616275/ /pubmed/37726420 http://dx.doi.org/10.1038/s41423-023-01083-0 Text en © The Author(s) 2023, corrected publication 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Neto, Tertuliano Alves Pereira
Sidney, John
Grifoni, Alba
Sette, Alessandro
Correlative CD4 and CD8 T-cell immunodominance in humans and mice: Implications for preclinical testing
title Correlative CD4 and CD8 T-cell immunodominance in humans and mice: Implications for preclinical testing
title_full Correlative CD4 and CD8 T-cell immunodominance in humans and mice: Implications for preclinical testing
title_fullStr Correlative CD4 and CD8 T-cell immunodominance in humans and mice: Implications for preclinical testing
title_full_unstemmed Correlative CD4 and CD8 T-cell immunodominance in humans and mice: Implications for preclinical testing
title_short Correlative CD4 and CD8 T-cell immunodominance in humans and mice: Implications for preclinical testing
title_sort correlative cd4 and cd8 t-cell immunodominance in humans and mice: implications for preclinical testing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616275/
https://www.ncbi.nlm.nih.gov/pubmed/37726420
http://dx.doi.org/10.1038/s41423-023-01083-0
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