Defining the HLA class I-associated viral antigen repertoire from HIV-1-infected human cells

Nicola Ternette, Hongbing Yang, Thomas Partridge, Aunska Llano, Samandhy Cedeno, Roman Fischer, Philip D Charles, Nadine L Dudek, Beatriz Mothe, Manuel Crespo, William M Fischer, Bette Korber, Morten Nielsen, Persephone Borrow, Anthony W Purcell, Christian Brander, Lucy Dorrell, Benedikt M Kessler, Tomas Hanke

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Recognition and eradication of infected cells by cytotoxic T lymphocytes is a key defense mechanism against intracellular pathogens. High-throughput definition of HLA class I-associated immunopeptidomes by mass spectrometry is an increasingly important analytical tool to advance our understanding of the induction of T cell responses against pathogens such as HIV-1. We utilized a liquid chromatography tandem mass spectrometry workflow including de novo-assisted database searching to define the HLA class I-associated immunopeptidome of HIV-1-infected human cells. We here report for the first time the identification of 75 HIV-1-derived peptides bound to HLA class I complexes that were purified directly from HIV-1-infected human primary CD4+ T cells and the C8166 human T cell line. Importantly, one third of eluted HIV-1 peptides had not been previously known to be presented by HLA class I. Over 82 of the identified sequences originated from viral protein regions for which T cell responses have previously been reported but for which the precise HLA class I binding sequences have not yet been defined. These results validate and expand the current knowledge of virus-specific antigenic peptide presentation during HIV-1 infection and provide novel targets for T cell vaccine development. This article is protected by copyright. All rights reserved.
Original languageEnglish
Pages (from-to)60-69
Number of pages10
JournalEuropean Journal of Immunology
Volume46
Issue number1
DOIs
Publication statusPublished - 2016

Cite this

Ternette, N., Yang, H., Partridge, T., Llano, A., Cedeno, S., Fischer, R., ... Hanke, T. (2016). Defining the HLA class I-associated viral antigen repertoire from HIV-1-infected human cells. European Journal of Immunology, 46(1), 60-69. https://doi.org/10.1002/eji.201545890
Ternette, Nicola ; Yang, Hongbing ; Partridge, Thomas ; Llano, Aunska ; Cedeno, Samandhy ; Fischer, Roman ; Charles, Philip D ; Dudek, Nadine L ; Mothe, Beatriz ; Crespo, Manuel ; Fischer, William M ; Korber, Bette ; Nielsen, Morten ; Borrow, Persephone ; Purcell, Anthony W ; Brander, Christian ; Dorrell, Lucy ; Kessler, Benedikt M ; Hanke, Tomas. / Defining the HLA class I-associated viral antigen repertoire from HIV-1-infected human cells. In: European Journal of Immunology. 2016 ; Vol. 46, No. 1. pp. 60-69.
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title = "Defining the HLA class I-associated viral antigen repertoire from HIV-1-infected human cells",
abstract = "Recognition and eradication of infected cells by cytotoxic T lymphocytes is a key defense mechanism against intracellular pathogens. High-throughput definition of HLA class I-associated immunopeptidomes by mass spectrometry is an increasingly important analytical tool to advance our understanding of the induction of T cell responses against pathogens such as HIV-1. We utilized a liquid chromatography tandem mass spectrometry workflow including de novo-assisted database searching to define the HLA class I-associated immunopeptidome of HIV-1-infected human cells. We here report for the first time the identification of 75 HIV-1-derived peptides bound to HLA class I complexes that were purified directly from HIV-1-infected human primary CD4+ T cells and the C8166 human T cell line. Importantly, one third of eluted HIV-1 peptides had not been previously known to be presented by HLA class I. Over 82 of the identified sequences originated from viral protein regions for which T cell responses have previously been reported but for which the precise HLA class I binding sequences have not yet been defined. These results validate and expand the current knowledge of virus-specific antigenic peptide presentation during HIV-1 infection and provide novel targets for T cell vaccine development. This article is protected by copyright. All rights reserved.",
author = "Nicola Ternette and Hongbing Yang and Thomas Partridge and Aunska Llano and Samandhy Cedeno and Roman Fischer and Charles, {Philip D} and Dudek, {Nadine L} and Beatriz Mothe and Manuel Crespo and Fischer, {William M} and Bette Korber and Morten Nielsen and Persephone Borrow and Purcell, {Anthony W} and Christian Brander and Lucy Dorrell and Kessler, {Benedikt M} and Tomas Hanke",
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Ternette, N, Yang, H, Partridge, T, Llano, A, Cedeno, S, Fischer, R, Charles, PD, Dudek, NL, Mothe, B, Crespo, M, Fischer, WM, Korber, B, Nielsen, M, Borrow, P, Purcell, AW, Brander, C, Dorrell, L, Kessler, BM & Hanke, T 2016, 'Defining the HLA class I-associated viral antigen repertoire from HIV-1-infected human cells' European Journal of Immunology, vol. 46, no. 1, pp. 60-69. https://doi.org/10.1002/eji.201545890

Defining the HLA class I-associated viral antigen repertoire from HIV-1-infected human cells. / Ternette, Nicola; Yang, Hongbing; Partridge, Thomas; Llano, Aunska; Cedeno, Samandhy; Fischer, Roman; Charles, Philip D; Dudek, Nadine L; Mothe, Beatriz; Crespo, Manuel; Fischer, William M; Korber, Bette; Nielsen, Morten; Borrow, Persephone; Purcell, Anthony W; Brander, Christian; Dorrell, Lucy; Kessler, Benedikt M; Hanke, Tomas.

In: European Journal of Immunology, Vol. 46, No. 1, 2016, p. 60-69.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Defining the HLA class I-associated viral antigen repertoire from HIV-1-infected human cells

AU - Ternette, Nicola

AU - Yang, Hongbing

AU - Partridge, Thomas

AU - Llano, Aunska

AU - Cedeno, Samandhy

AU - Fischer, Roman

AU - Charles, Philip D

AU - Dudek, Nadine L

AU - Mothe, Beatriz

AU - Crespo, Manuel

AU - Fischer, William M

AU - Korber, Bette

AU - Nielsen, Morten

AU - Borrow, Persephone

AU - Purcell, Anthony W

AU - Brander, Christian

AU - Dorrell, Lucy

AU - Kessler, Benedikt M

AU - Hanke, Tomas

PY - 2016

Y1 - 2016

N2 - Recognition and eradication of infected cells by cytotoxic T lymphocytes is a key defense mechanism against intracellular pathogens. High-throughput definition of HLA class I-associated immunopeptidomes by mass spectrometry is an increasingly important analytical tool to advance our understanding of the induction of T cell responses against pathogens such as HIV-1. We utilized a liquid chromatography tandem mass spectrometry workflow including de novo-assisted database searching to define the HLA class I-associated immunopeptidome of HIV-1-infected human cells. We here report for the first time the identification of 75 HIV-1-derived peptides bound to HLA class I complexes that were purified directly from HIV-1-infected human primary CD4+ T cells and the C8166 human T cell line. Importantly, one third of eluted HIV-1 peptides had not been previously known to be presented by HLA class I. Over 82 of the identified sequences originated from viral protein regions for which T cell responses have previously been reported but for which the precise HLA class I binding sequences have not yet been defined. These results validate and expand the current knowledge of virus-specific antigenic peptide presentation during HIV-1 infection and provide novel targets for T cell vaccine development. This article is protected by copyright. All rights reserved.

AB - Recognition and eradication of infected cells by cytotoxic T lymphocytes is a key defense mechanism against intracellular pathogens. High-throughput definition of HLA class I-associated immunopeptidomes by mass spectrometry is an increasingly important analytical tool to advance our understanding of the induction of T cell responses against pathogens such as HIV-1. We utilized a liquid chromatography tandem mass spectrometry workflow including de novo-assisted database searching to define the HLA class I-associated immunopeptidome of HIV-1-infected human cells. We here report for the first time the identification of 75 HIV-1-derived peptides bound to HLA class I complexes that were purified directly from HIV-1-infected human primary CD4+ T cells and the C8166 human T cell line. Importantly, one third of eluted HIV-1 peptides had not been previously known to be presented by HLA class I. Over 82 of the identified sequences originated from viral protein regions for which T cell responses have previously been reported but for which the precise HLA class I binding sequences have not yet been defined. These results validate and expand the current knowledge of virus-specific antigenic peptide presentation during HIV-1 infection and provide novel targets for T cell vaccine development. This article is protected by copyright. All rights reserved.

UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737398/pdf/EJI-46-60.pdf

U2 - 10.1002/eji.201545890

DO - 10.1002/eji.201545890

M3 - Article

VL - 46

SP - 60

EP - 69

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 1

ER -