Tapasin-mediated editing of the MHC I immunopeptidome is epitope specific and dependent on peptide off-rate, abundance, and level of tapasin expression.
antigen presentation
immunopeptidome
interferon-γ
major histocompatibility class I
peptide repertoire
tapasin
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2022
2022
Historique:
received:
30
05
2022
accepted:
27
09
2022
entrez:
17
11
2022
pubmed:
18
11
2022
medline:
22
11
2022
Statut:
epublish
Résumé
Tapasin, a component of the major histocompatibility complex (MHC) I peptide loading complex, edits the repertoire of peptides that is presented at the cell surface by MHC I and thereby plays a key role in shaping the hierarchy of CD8+ T-cell responses to tumors and pathogens. We have developed a system that allows us to tune the level of tapasin expression and independently regulate the expression of competing peptides of different off-rates. By quantifying the relative surface expression of peptides presented by MHC I molecules, we show that peptide editing by tapasin can be measured in terms of "tapasin bonus," which is dependent on both peptide kinetic stability (off-rate) and peptide abundance (peptide supply). Each peptide has therefore an individual tapasin bonus fingerprint. We also show that there is an optimal level of tapasin expression for each peptide in the immunopeptidome, dependent on its off-rate and abundance. This is important, as the level of tapasin expression can vary widely during different stages of the immune response against pathogens or cancer and is often the target for immune escape.
Identifiants
pubmed: 36389776
doi: 10.3389/fimmu.2022.956603
pmc: PMC9659924
doi:
Substances chimiques
tapasin
0
Epitopes
0
Histocompatibility Antigens Class I
0
Peptides
0
Histocompatibility Antigens
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
956603Informations de copyright
Copyright © 2022 Boulanger, Douglas, Duriez, Kang, Dalchau, James and Elliott.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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