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ARTEMIS: A Novel Mass-Spec Platform for HLA-Restricted Self and Disease-Associated Peptide Discovery

Conventional immunoprecipitation/mass spectroscopy identification of HLA-restricted peptides remains the purview of specializing laboratories, due to the complexity of the methodology, and requires computational post-analysis to assign peptides to individual alleles when using pan-HLA antibodies. We...

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Autores principales: Finton, Kathryn A. K., Brusniak, Mi-Youn, Jones, Lisa A., Lin, Chenwei, Fioré-Gartland, Andrew J., Brock, Chance, Gafken, Philip R., Strong, Roland K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111693/
https://www.ncbi.nlm.nih.gov/pubmed/33986749
http://dx.doi.org/10.3389/fimmu.2021.658372
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author Finton, Kathryn A. K.
Brusniak, Mi-Youn
Jones, Lisa A.
Lin, Chenwei
Fioré-Gartland, Andrew J.
Brock, Chance
Gafken, Philip R.
Strong, Roland K.
author_facet Finton, Kathryn A. K.
Brusniak, Mi-Youn
Jones, Lisa A.
Lin, Chenwei
Fioré-Gartland, Andrew J.
Brock, Chance
Gafken, Philip R.
Strong, Roland K.
author_sort Finton, Kathryn A. K.
collection PubMed
description Conventional immunoprecipitation/mass spectroscopy identification of HLA-restricted peptides remains the purview of specializing laboratories, due to the complexity of the methodology, and requires computational post-analysis to assign peptides to individual alleles when using pan-HLA antibodies. We have addressed these limitations with ARTEMIS: a simple, robust, and flexible platform for peptide discovery across ligandomes, optionally including specific proteins-of-interest, that combines novel, secreted HLA-I discovery reagents spanning multiple alleles, optimized lentiviral transduction, and streamlined affinity-tag purification to improve upon conventional methods. This platform fills a middle ground between existing techniques: sensitive and adaptable, but easy and affordable enough to be widely employed by general laboratories. We used ARTEMIS to catalog allele-specific ligandomes from HEK293 cells for seven classical HLA alleles and compared results across replicates, against computational predictions, and against high-quality conventional datasets. We also applied ARTEMIS to identify potentially useful, novel HLA-restricted peptide targets from oncovirus oncoproteins and tumor-associated antigens.
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spelling pubmed-81116932021-05-12 ARTEMIS: A Novel Mass-Spec Platform for HLA-Restricted Self and Disease-Associated Peptide Discovery Finton, Kathryn A. K. Brusniak, Mi-Youn Jones, Lisa A. Lin, Chenwei Fioré-Gartland, Andrew J. Brock, Chance Gafken, Philip R. Strong, Roland K. Front Immunol Immunology Conventional immunoprecipitation/mass spectroscopy identification of HLA-restricted peptides remains the purview of specializing laboratories, due to the complexity of the methodology, and requires computational post-analysis to assign peptides to individual alleles when using pan-HLA antibodies. We have addressed these limitations with ARTEMIS: a simple, robust, and flexible platform for peptide discovery across ligandomes, optionally including specific proteins-of-interest, that combines novel, secreted HLA-I discovery reagents spanning multiple alleles, optimized lentiviral transduction, and streamlined affinity-tag purification to improve upon conventional methods. This platform fills a middle ground between existing techniques: sensitive and adaptable, but easy and affordable enough to be widely employed by general laboratories. We used ARTEMIS to catalog allele-specific ligandomes from HEK293 cells for seven classical HLA alleles and compared results across replicates, against computational predictions, and against high-quality conventional datasets. We also applied ARTEMIS to identify potentially useful, novel HLA-restricted peptide targets from oncovirus oncoproteins and tumor-associated antigens. Frontiers Media S.A. 2021-04-23 /pmc/articles/PMC8111693/ /pubmed/33986749 http://dx.doi.org/10.3389/fimmu.2021.658372 Text en Copyright © 2021 Finton, Brusniak, Jones, Lin, Fioré-Gartland, Brock, Gafken and Strong https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Finton, Kathryn A. K.
Brusniak, Mi-Youn
Jones, Lisa A.
Lin, Chenwei
Fioré-Gartland, Andrew J.
Brock, Chance
Gafken, Philip R.
Strong, Roland K.
ARTEMIS: A Novel Mass-Spec Platform for HLA-Restricted Self and Disease-Associated Peptide Discovery
title ARTEMIS: A Novel Mass-Spec Platform for HLA-Restricted Self and Disease-Associated Peptide Discovery
title_full ARTEMIS: A Novel Mass-Spec Platform for HLA-Restricted Self and Disease-Associated Peptide Discovery
title_fullStr ARTEMIS: A Novel Mass-Spec Platform for HLA-Restricted Self and Disease-Associated Peptide Discovery
title_full_unstemmed ARTEMIS: A Novel Mass-Spec Platform for HLA-Restricted Self and Disease-Associated Peptide Discovery
title_short ARTEMIS: A Novel Mass-Spec Platform for HLA-Restricted Self and Disease-Associated Peptide Discovery
title_sort artemis: a novel mass-spec platform for hla-restricted self and disease-associated peptide discovery
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111693/
https://www.ncbi.nlm.nih.gov/pubmed/33986749
http://dx.doi.org/10.3389/fimmu.2021.658372
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