Absolute quantification of tumor antigens using embedded MHC-I isotopologue calibrants.
MHC class I
antigen presentation
immunopeptidomics
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
14 09 2021
14 09 2021
Historique:
accepted:
02
08
2021
entrez:
9
9
2021
pubmed:
10
9
2021
medline:
15
12
2021
Statut:
ppublish
Résumé
Absolute quantification measurements (copies per cell) of peptide major histocompatibility complex (pMHC) antigens are necessary to inform targeted immunotherapy drug design; however, existing methods for absolute quantification have critical limitations. Here, we present a platform termed SureQuant-IsoMHC, utilizing a series of pMHC isotopologues and internal standard-triggered targeted mass spectrometry to generate an embedded multipoint calibration curve to determine endogenous pMHC concentrations for a panel of 18 tumor antigens. We apply SureQuant-IsoMHC to measure changes in expression of our target panel in a melanoma cell line treated with a MEK inhibitor and translate this approach to estimate antigen concentrations in melanoma tumor biopsies.
Identifiants
pubmed: 34497125
pii: 2111173118
doi: 10.1073/pnas.2111173118
pmc: PMC8449407
pii:
doi:
Substances chimiques
Antigens, Neoplasm
0
Benzimidazoles
0
Histocompatibility Antigens Class I
0
binimetinib
181R97MR71
MAP Kinase Kinase 1
EC 2.7.12.2
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
Subventions
Organisme : NIEHS NIH HHS
ID : T32 ES007020
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA238720
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA210180
Pays : United States
Informations de copyright
Copyright © 2021 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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