Identification of HLA-E Binding Mycobacterium tuberculosis–Derived Epitopes through Improved Prediction Models
The Journal of Immunology, vol. 209, pp. 1555–1565
Abstract
Abstract Tuberculosis (TB) remains one of the deadliest infectious diseases worldwide, posing great social and economic burden to affected countries. Novel vaccine approaches are needed to increase protective immunity against the causative agent Mycobacterium tuberculosis (Mtb) and to reduce the development of active TB disease in latently infected individuals. Donor-unrestricted T cell responses represent such novel potential vaccine targets. HLA-E-restricted T cell responses have been shown to play an important role in protection against TB and other infections, and recent studies have demonstrated that these cells can be primed in vitro. However, the identification of novel pathogen-derived HLA-E binding peptides presented by infected target cells has been limited by the lack of accurate prediction algorithms for HLA-E binding. In this study, we developed an improved HLA-E binding peptide prediction algorithm and implemented it to identify (to our knowledge) novel Mtb-derived peptides with capacity to induce CD8+ T cell activation and that were recognized by specific HLA-E-restricted T cells in Mycobacterium-exposed humans. Altogether, we present a novel algorithm for the identification of pathogen- or self-derived HLA-E-presented peptides.
Authors 17
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Leiden University Medical Center
Affiliation as printed
Department of Infectious Diseases, Leiden University Medical Center , Leiden,
*Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands;
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Leiden University Medical Center
Affiliation as printed
Department of Infectious Diseases, Leiden University Medical Center , Leiden,
*Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands;
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Leiden University Medical Center
Affiliation as printed
Department of Infectious Diseases, Leiden University Medical Center , Leiden,
*Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands;
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Leiden University Medical Center
Affiliation as printed
Department of Infectious Diseases, Leiden University Medical Center , Leiden,
*Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands;
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Leiden University Medical Center
Affiliation as printed
Department of Cell and Chemical Biology, Leiden University Medical Center , Leiden,
†Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands;
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Leiden University Medical Center
Affiliation as printed
Department of Dermatology, Leiden University Medical Center , Leiden,
‡Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands;
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Leiden University Medical Center
Affiliation as printed
Center for Proteomics and Metabolomics, Leiden University Medical Center , Leiden,
§Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands;
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Leiden University Medical Center
Affiliation as printed
Center for Proteomics and Metabolomics, Leiden University Medical Center , Leiden,
§Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands;
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Affiliation as printed
Research and Development Department, UK Health Security Agency , Salisbury,
¶Research and Development Department, UK Health Security Agency, Salisbury, United Kingdom;
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Affiliation as printed
Research and Development Department, UK Health Security Agency , Salisbury,
¶Research and Development Department, UK Health Security Agency, Salisbury, United Kingdom;
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Affiliation as printed
Research and Development Department, UK Health Security Agency , Salisbury,
¶Research and Development Department, UK Health Security Agency, Salisbury, United Kingdom;
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Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani
Affiliation as printed
National Institute for Infectious Diseases Lazzaro Spallanzani Scientific Institute for Research, Hospitalization and Healthcare , Rome,
‖National Institute for Infectious Diseases Lazzaro Spallanzani Scientific Institute for Research, Hospitalization and Healthcare, Rome, Italy;
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Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani
Affiliation as printed
National Institute for Infectious Diseases Lazzaro Spallanzani Scientific Institute for Research, Hospitalization and Healthcare , Rome,
‖National Institute for Infectious Diseases Lazzaro Spallanzani Scientific Institute for Research, Hospitalization and Healthcare, Rome, Italy;
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Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani
Affiliation as printed
National Institute for Infectious Diseases Lazzaro Spallanzani Scientific Institute for Research, Hospitalization and Healthcare , Rome,
‖National Institute for Infectious Diseases Lazzaro Spallanzani Scientific Institute for Research, Hospitalization and Healthcare, Rome, Italy;
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Broad Institute · Delft University of Technology
Affiliation as printed
Delft Bioinformatics Lab, Delft University of Technology , Delft,
Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard , Cambridge, MA
#Delft Bioinformatics Lab, Delft University of Technology, Delft, the Netherlands; and
**Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA
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Leiden University Medical Center
Affiliation as printed
Department of Infectious Diseases, Leiden University Medical Center , Leiden,
*Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands;
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Leiden University Medical Center
Affiliation as printed
Department of Infectious Diseases, Leiden University Medical Center , Leiden,
*Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands;
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