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Pathogen-derived HLA-E bound epitopes reveal broad primary anchor pocket tolerability and conformationally malleable peptide binding
Through major histocompatibility complex class Ia leader sequence-derived (VL9) peptide binding and CD94/NKG2 receptor engagement, human leucocyte antigen E (HLA-E) reports cellular health to NK cells. Previous studies demonstrated a strong bias for VL9 binding by HLA-E, a preference subsequently su...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6081459/ https://www.ncbi.nlm.nih.gov/pubmed/30087334 http://dx.doi.org/10.1038/s41467-018-05459-z |
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author | Walters, Lucy C. Harlos, Karl Brackenridge, Simon Rozbesky, Daniel Barrett, Jordan R. Jain, Vitul Walter, Thomas S. O’Callaghan, Chris A. Borrow, Persephone Toebes, Mireille Hansen, Scott G. Sacha, Jonah B Abdulhaqq, Shaheed Greene, Justin M. Früh, Klaus Marshall, Emily Picker, Louis J. Jones, E. Yvonne McMichael, Andrew J. Gillespie, Geraldine M. |
author_facet | Walters, Lucy C. Harlos, Karl Brackenridge, Simon Rozbesky, Daniel Barrett, Jordan R. Jain, Vitul Walter, Thomas S. O’Callaghan, Chris A. Borrow, Persephone Toebes, Mireille Hansen, Scott G. Sacha, Jonah B Abdulhaqq, Shaheed Greene, Justin M. Früh, Klaus Marshall, Emily Picker, Louis J. Jones, E. Yvonne McMichael, Andrew J. Gillespie, Geraldine M. |
author_sort | Walters, Lucy C. |
collection | PubMed |
description | Through major histocompatibility complex class Ia leader sequence-derived (VL9) peptide binding and CD94/NKG2 receptor engagement, human leucocyte antigen E (HLA-E) reports cellular health to NK cells. Previous studies demonstrated a strong bias for VL9 binding by HLA-E, a preference subsequently supported by structural analyses. However, Mycobacteria tuberculosis (Mtb) infection and Rhesus cytomegalovirus-vectored SIV vaccinations revealed contexts where HLA-E and the rhesus homologue, Mamu-E, presented diverse pathogen-derived peptides to CD8(+) T cells, respectively. Here we present crystal structures of HLA-E in complex with HIV and Mtb-derived peptides. We show that despite the presence of preferred primary anchor residues, HLA-E-bound peptides can adopt alternative conformations within the peptide binding groove. Furthermore, combined structural and mutagenesis analyses illustrate a greater tolerance for hydrophobic and polar residues in the primary pockets than previously appreciated. Finally, biochemical studies reveal HLA-E peptide binding and exchange characteristics with potential relevance to its alternative antigen presenting function in vivo. |
format | Online Article Text |
id | pubmed-6081459 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60814592018-08-09 Pathogen-derived HLA-E bound epitopes reveal broad primary anchor pocket tolerability and conformationally malleable peptide binding Walters, Lucy C. Harlos, Karl Brackenridge, Simon Rozbesky, Daniel Barrett, Jordan R. Jain, Vitul Walter, Thomas S. O’Callaghan, Chris A. Borrow, Persephone Toebes, Mireille Hansen, Scott G. Sacha, Jonah B Abdulhaqq, Shaheed Greene, Justin M. Früh, Klaus Marshall, Emily Picker, Louis J. Jones, E. Yvonne McMichael, Andrew J. Gillespie, Geraldine M. Nat Commun Article Through major histocompatibility complex class Ia leader sequence-derived (VL9) peptide binding and CD94/NKG2 receptor engagement, human leucocyte antigen E (HLA-E) reports cellular health to NK cells. Previous studies demonstrated a strong bias for VL9 binding by HLA-E, a preference subsequently supported by structural analyses. However, Mycobacteria tuberculosis (Mtb) infection and Rhesus cytomegalovirus-vectored SIV vaccinations revealed contexts where HLA-E and the rhesus homologue, Mamu-E, presented diverse pathogen-derived peptides to CD8(+) T cells, respectively. Here we present crystal structures of HLA-E in complex with HIV and Mtb-derived peptides. We show that despite the presence of preferred primary anchor residues, HLA-E-bound peptides can adopt alternative conformations within the peptide binding groove. Furthermore, combined structural and mutagenesis analyses illustrate a greater tolerance for hydrophobic and polar residues in the primary pockets than previously appreciated. Finally, biochemical studies reveal HLA-E peptide binding and exchange characteristics with potential relevance to its alternative antigen presenting function in vivo. Nature Publishing Group UK 2018-08-07 /pmc/articles/PMC6081459/ /pubmed/30087334 http://dx.doi.org/10.1038/s41467-018-05459-z Text en © The Author(s) 2018 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Walters, Lucy C. Harlos, Karl Brackenridge, Simon Rozbesky, Daniel Barrett, Jordan R. Jain, Vitul Walter, Thomas S. O’Callaghan, Chris A. Borrow, Persephone Toebes, Mireille Hansen, Scott G. Sacha, Jonah B Abdulhaqq, Shaheed Greene, Justin M. Früh, Klaus Marshall, Emily Picker, Louis J. Jones, E. Yvonne McMichael, Andrew J. Gillespie, Geraldine M. Pathogen-derived HLA-E bound epitopes reveal broad primary anchor pocket tolerability and conformationally malleable peptide binding |
title | Pathogen-derived HLA-E bound epitopes reveal broad primary anchor pocket tolerability and conformationally malleable peptide binding |
title_full | Pathogen-derived HLA-E bound epitopes reveal broad primary anchor pocket tolerability and conformationally malleable peptide binding |
title_fullStr | Pathogen-derived HLA-E bound epitopes reveal broad primary anchor pocket tolerability and conformationally malleable peptide binding |
title_full_unstemmed | Pathogen-derived HLA-E bound epitopes reveal broad primary anchor pocket tolerability and conformationally malleable peptide binding |
title_short | Pathogen-derived HLA-E bound epitopes reveal broad primary anchor pocket tolerability and conformationally malleable peptide binding |
title_sort | pathogen-derived hla-e bound epitopes reveal broad primary anchor pocket tolerability and conformationally malleable peptide binding |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6081459/ https://www.ncbi.nlm.nih.gov/pubmed/30087334 http://dx.doi.org/10.1038/s41467-018-05459-z |
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