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High-resolution profiling of MHC II peptide presentation capacity reveals SARS-CoV-2 CD4 T cell targets and mechanisms of immune escape

Understanding peptide presentation by specific MHC alleles is fundamental for controlling physiological functions of T cells and harnessing them for therapeutic use. However, commonly used in silico predictions and mass spectroscopy have their limitations in precision, sensitivity, and throughput, p...

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Autores principales: Obermair, Franz-Josef, Renoux, Florian, Heer, Sebastian, Lee, Chloe H., Cereghetti, Nastassja, Loi, Marisa, Maestri, Giulia, Haldner, Yannick, Wuigk, Robin, Iosefson, Ohad, Patel, Pooja, Triebel, Katherine, Kopf, Manfred, Swain, Joanna, Kisielow, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9054008/
https://www.ncbi.nlm.nih.gov/pubmed/35486722
http://dx.doi.org/10.1126/sciadv.abl5394
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author Obermair, Franz-Josef
Renoux, Florian
Heer, Sebastian
Lee, Chloe H.
Cereghetti, Nastassja
Loi, Marisa
Maestri, Giulia
Haldner, Yannick
Wuigk, Robin
Iosefson, Ohad
Patel, Pooja
Triebel, Katherine
Kopf, Manfred
Swain, Joanna
Kisielow, Jan
author_facet Obermair, Franz-Josef
Renoux, Florian
Heer, Sebastian
Lee, Chloe H.
Cereghetti, Nastassja
Loi, Marisa
Maestri, Giulia
Haldner, Yannick
Wuigk, Robin
Iosefson, Ohad
Patel, Pooja
Triebel, Katherine
Kopf, Manfred
Swain, Joanna
Kisielow, Jan
author_sort Obermair, Franz-Josef
collection PubMed
description Understanding peptide presentation by specific MHC alleles is fundamental for controlling physiological functions of T cells and harnessing them for therapeutic use. However, commonly used in silico predictions and mass spectroscopy have their limitations in precision, sensitivity, and throughput, particularly for MHC class II. Here, we present MEDi, a novel mammalian epitope display that allows an unbiased, affordable, high-resolution mapping of MHC peptide presentation capacity. Our platform provides a detailed picture by testing every antigen-derived peptide and is scalable to all the MHC II alleles. Given the urgent need to understand immune evasion for formulating effective responses to threats such as SARS-CoV-2, we provide a comprehensive analysis of the presentability of all SARS-CoV-2 peptides in the context of several HLA class II alleles. We show that several mutations arising in viral strains expanding globally resulted in reduced peptide presentability by multiple HLA class II alleles, while some increased it, suggesting alteration of MHC II presentation landscapes as a possible immune escape mechanism.
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spelling pubmed-90540082022-05-04 High-resolution profiling of MHC II peptide presentation capacity reveals SARS-CoV-2 CD4 T cell targets and mechanisms of immune escape Obermair, Franz-Josef Renoux, Florian Heer, Sebastian Lee, Chloe H. Cereghetti, Nastassja Loi, Marisa Maestri, Giulia Haldner, Yannick Wuigk, Robin Iosefson, Ohad Patel, Pooja Triebel, Katherine Kopf, Manfred Swain, Joanna Kisielow, Jan Sci Adv Biomedicine and Life Sciences Understanding peptide presentation by specific MHC alleles is fundamental for controlling physiological functions of T cells and harnessing them for therapeutic use. However, commonly used in silico predictions and mass spectroscopy have their limitations in precision, sensitivity, and throughput, particularly for MHC class II. Here, we present MEDi, a novel mammalian epitope display that allows an unbiased, affordable, high-resolution mapping of MHC peptide presentation capacity. Our platform provides a detailed picture by testing every antigen-derived peptide and is scalable to all the MHC II alleles. Given the urgent need to understand immune evasion for formulating effective responses to threats such as SARS-CoV-2, we provide a comprehensive analysis of the presentability of all SARS-CoV-2 peptides in the context of several HLA class II alleles. We show that several mutations arising in viral strains expanding globally resulted in reduced peptide presentability by multiple HLA class II alleles, while some increased it, suggesting alteration of MHC II presentation landscapes as a possible immune escape mechanism. American Association for the Advancement of Science 2022-04-29 /pmc/articles/PMC9054008/ /pubmed/35486722 http://dx.doi.org/10.1126/sciadv.abl5394 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Biomedicine and Life Sciences
Obermair, Franz-Josef
Renoux, Florian
Heer, Sebastian
Lee, Chloe H.
Cereghetti, Nastassja
Loi, Marisa
Maestri, Giulia
Haldner, Yannick
Wuigk, Robin
Iosefson, Ohad
Patel, Pooja
Triebel, Katherine
Kopf, Manfred
Swain, Joanna
Kisielow, Jan
High-resolution profiling of MHC II peptide presentation capacity reveals SARS-CoV-2 CD4 T cell targets and mechanisms of immune escape
title High-resolution profiling of MHC II peptide presentation capacity reveals SARS-CoV-2 CD4 T cell targets and mechanisms of immune escape
title_full High-resolution profiling of MHC II peptide presentation capacity reveals SARS-CoV-2 CD4 T cell targets and mechanisms of immune escape
title_fullStr High-resolution profiling of MHC II peptide presentation capacity reveals SARS-CoV-2 CD4 T cell targets and mechanisms of immune escape
title_full_unstemmed High-resolution profiling of MHC II peptide presentation capacity reveals SARS-CoV-2 CD4 T cell targets and mechanisms of immune escape
title_short High-resolution profiling of MHC II peptide presentation capacity reveals SARS-CoV-2 CD4 T cell targets and mechanisms of immune escape
title_sort high-resolution profiling of mhc ii peptide presentation capacity reveals sars-cov-2 cd4 t cell targets and mechanisms of immune escape
topic Biomedicine and Life Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9054008/
https://www.ncbi.nlm.nih.gov/pubmed/35486722
http://dx.doi.org/10.1126/sciadv.abl5394
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