HLA-II immunopeptidome profiling and deep learning reveal features of antigenicity to inform antigen discovery.
CD4(+) T cells
MHC class II
SARS-CoV-2 antigens
antigen presentation
immunopeptidomics
microbiome antigens
protein sequence models
Journal
Immunity
ISSN: 1097-4180
Titre abrégé: Immunity
Pays: United States
ID NLM: 9432918
Informations de publication
Date de publication:
11 07 2023
11 07 2023
Historique:
received:
25
08
2022
revised:
08
02
2023
accepted:
11
05
2023
pmc-release:
11
07
2024
medline:
14
7
2023
pubmed:
11
6
2023
entrez:
10
6
2023
Statut:
ppublish
Résumé
CD4+ T cell responses are exquisitely antigen specific and directed toward peptide epitopes displayed by human leukocyte antigen class II (HLA-II) on antigen-presenting cells. Underrepresentation of diverse alleles in ligand databases and an incomplete understanding of factors affecting antigen presentation in vivo have limited progress in defining principles of peptide immunogenicity. Here, we employed monoallelic immunopeptidomics to identify 358,024 HLA-II binders, with a particular focus on HLA-DQ and HLA-DP. We uncovered peptide-binding patterns across a spectrum of binding affinities and enrichment of structural antigen features. These aspects underpinned the development of context-aware predictor of T cell antigens (CAPTAn), a deep learning model that predicts peptide antigens based on their affinity to HLA-II and full sequence of their source proteins. CAPTAn was instrumental in discovering prevalent T cell epitopes from bacteria in the human microbiome and a pan-variant epitope from SARS-CoV-2. Together CAPTAn and associated datasets present a resource for antigen discovery and the unraveling genetic associations of HLA alleles with immunopathologies.
Identifiants
pubmed: 37301199
pii: S1074-7613(23)00226-1
doi: 10.1016/j.immuni.2023.05.009
pmc: PMC10519123
mid: NIHMS1903185
pii:
doi:
Substances chimiques
Captan
EOL5G26Q9F
HLA Antigens
0
Epitopes, T-Lymphocyte
0
Peptides
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1681-1698.e13Subventions
Organisme : NIAID NIH HHS
ID : U19 AI110495
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK043351
Pays : United States
Organisme : NIDDK NIH HHS
ID : RC2 DK114784
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA271075
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA270823
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA206978
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests R.J.X. is a co-founder of Celsius Therapeutics and Jnana Therapeutics, a member of the Scientific Advisory Board at Nestle, and a member of the Board of Directors at Moonlake Immunotherapeutics. S.A.C. is a member of the scientific advisory boards of Kymera, PTM BioLabs, Seer, and PrognomIQ.
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