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Use of HLA peptidomics and whole exome sequencing to identify human immunogenic neo-antigens
The antigenicity of cells is demarcated by the peptides bound by their Human Leucocyte Antigen (HLA) molecules. Through this antigen presentation, T cell specificity response is controlled. As a fraction of the expressed mutated peptides is presented on the HLA, these neo-epitopes could be immunogen...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4868674/ https://www.ncbi.nlm.nih.gov/pubmed/26819371 http://dx.doi.org/10.18632/oncotarget.6960 |
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author | Kalaora, Shelly Barnea, Eilon Merhavi-Shoham, Efrat Qutob, Nouar Teer, Jamie K. Shimony, Nilly Schachter, Jacob Rosenberg, Steven A. Besser, Michal J. Admon, Arie Samuels, Yardena |
author_facet | Kalaora, Shelly Barnea, Eilon Merhavi-Shoham, Efrat Qutob, Nouar Teer, Jamie K. Shimony, Nilly Schachter, Jacob Rosenberg, Steven A. Besser, Michal J. Admon, Arie Samuels, Yardena |
author_sort | Kalaora, Shelly |
collection | PubMed |
description | The antigenicity of cells is demarcated by the peptides bound by their Human Leucocyte Antigen (HLA) molecules. Through this antigen presentation, T cell specificity response is controlled. As a fraction of the expressed mutated peptides is presented on the HLA, these neo-epitopes could be immunogenic. Such neoantigens have recently been identified through screening for predicted mutated peptides, using synthetic peptides or ones expressed from minigenes, combined with screening of patient tumor-infiltrating lymphocytes (TILs). Here we present a time and cost-effective method that combines whole-exome sequencing analysis with HLA peptidome mass spectrometry, to identify neo-antigens in a melanoma patient. Of the 1,019 amino acid changes identified through exome sequencing, two were confirmed by mass spectrometry to be presented by the cells. We then synthesized peptides and evaluated the two mutated neo-antigens for reactivity with autologous bulk TILs, and found that one yielded mutant-specific T-cell response. Our results demonstrate that this method can be used for immune response prediction and promise to provide an alternative approach for identifying immunogenic neo-epitopes in cancer. |
format | Online Article Text |
id | pubmed-4868674 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-48686742016-05-20 Use of HLA peptidomics and whole exome sequencing to identify human immunogenic neo-antigens Kalaora, Shelly Barnea, Eilon Merhavi-Shoham, Efrat Qutob, Nouar Teer, Jamie K. Shimony, Nilly Schachter, Jacob Rosenberg, Steven A. Besser, Michal J. Admon, Arie Samuels, Yardena Oncotarget Priority Research Paper The antigenicity of cells is demarcated by the peptides bound by their Human Leucocyte Antigen (HLA) molecules. Through this antigen presentation, T cell specificity response is controlled. As a fraction of the expressed mutated peptides is presented on the HLA, these neo-epitopes could be immunogenic. Such neoantigens have recently been identified through screening for predicted mutated peptides, using synthetic peptides or ones expressed from minigenes, combined with screening of patient tumor-infiltrating lymphocytes (TILs). Here we present a time and cost-effective method that combines whole-exome sequencing analysis with HLA peptidome mass spectrometry, to identify neo-antigens in a melanoma patient. Of the 1,019 amino acid changes identified through exome sequencing, two were confirmed by mass spectrometry to be presented by the cells. We then synthesized peptides and evaluated the two mutated neo-antigens for reactivity with autologous bulk TILs, and found that one yielded mutant-specific T-cell response. Our results demonstrate that this method can be used for immune response prediction and promise to provide an alternative approach for identifying immunogenic neo-epitopes in cancer. Impact Journals LLC 2016-01-20 /pmc/articles/PMC4868674/ /pubmed/26819371 http://dx.doi.org/10.18632/oncotarget.6960 Text en Copyright: © 2016 Kalaora et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Priority Research Paper Kalaora, Shelly Barnea, Eilon Merhavi-Shoham, Efrat Qutob, Nouar Teer, Jamie K. Shimony, Nilly Schachter, Jacob Rosenberg, Steven A. Besser, Michal J. Admon, Arie Samuels, Yardena Use of HLA peptidomics and whole exome sequencing to identify human immunogenic neo-antigens |
title | Use of HLA peptidomics and whole exome sequencing to identify human immunogenic neo-antigens |
title_full | Use of HLA peptidomics and whole exome sequencing to identify human immunogenic neo-antigens |
title_fullStr | Use of HLA peptidomics and whole exome sequencing to identify human immunogenic neo-antigens |
title_full_unstemmed | Use of HLA peptidomics and whole exome sequencing to identify human immunogenic neo-antigens |
title_short | Use of HLA peptidomics and whole exome sequencing to identify human immunogenic neo-antigens |
title_sort | use of hla peptidomics and whole exome sequencing to identify human immunogenic neo-antigens |
topic | Priority Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4868674/ https://www.ncbi.nlm.nih.gov/pubmed/26819371 http://dx.doi.org/10.18632/oncotarget.6960 |
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