Absolute quantification of tumor antigens using embedded MHC-I isotopologue calibrants.

TitleAbsolute quantification of tumor antigens using embedded MHC-I isotopologue calibrants.
Publication TypeJournal Article
Year of Publication2021
AuthorsStopfer LE, Gajadhar AS, Patel B, Gallien S, Frederick DT, Boland GM, Sullivan RJ, White FM
JournalProc Natl Acad Sci U S A
Volume118
Issue37
Date Published2021 Sep 14
ISSN1091-6490
Abstract

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.
DOI10.1073/pnas.2111173118
Alternate JournalProc Natl Acad Sci U S A
PubMed ID34497125