Thermal-exchange HLA-E multimers reveal specificity in HLA-E and NKG2A/CD94 complex interactions.
MHC/HLA
NK cell
T-cell
antigen presentation/processing
antigens/peptides/epitopes
Journal
Immunology
ISSN: 1365-2567
Titre abrégé: Immunology
Pays: England
ID NLM: 0374672
Informations de publication
Date de publication:
03 2023
03 2023
Historique:
received:
01
03
2022
accepted:
03
10
2022
pubmed:
12
10
2022
medline:
25
2
2023
entrez:
11
10
2022
Statut:
ppublish
Résumé
There is growing interest in HLA-E-restricted T-cell responses as a possible novel, highly conserved, vaccination targets in the context of infectious and malignant diseases. The developing field of HLA multimers for the detection and study of peptide-specific T cells has allowed the in-depth study of TCR repertoires and molecular requirements for efficient antigen presentation and T-cell activation. In this study, we developed a method for efficient peptide thermal exchange on HLA-E monomers and multimers allowing the high-throughput production of HLA-E multimers. We optimized the thermal-mediated peptide exchange, and flow cytometry staining conditions for the detection of TCR and NKG2A/CD94 receptors, showing that this novel approach can be used for high-throughput identification and analysis of HLA-E-binding peptides which could be involved in T-cell and NK cell-mediated immune responses. Importantly, our analysis of NKG2A/CD94 interaction in the presence of modified peptides led to new molecular insights governing the interaction of HLA-E with this receptor. In particular, our results reveal that interactions of HLA-E with NKG2A/CD94 and the TCR involve different residues. Altogether, we present a novel HLA-E multimer technology based on thermal-mediated peptide exchange allowing us to investigate the molecular requirements for HLA-E/peptide interaction with its receptors.
Substances chimiques
Histocompatibility Antigens Class I
0
Peptides
0
Receptors, Antigen, T-Cell
0
NK Cell Lectin-Like Receptor Subfamily D
0
NK Cell Lectin-Like Receptor Subfamily C
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
526-537Subventions
Organisme : NIAID NIH HHS
ID : R01 AI141315
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI127133
Pays : United States
Informations de copyright
© 2022 The Authors. Immunology published by John Wiley & Sons Ltd.
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