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Absolute quantification of tumor antigens using embedded MHC-I isotopologue calibrants
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Absolute quantification of tumor antigens using embedded MHC-I isotopologue calibrants
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Journal Article
Absolute quantification of tumor antigens using embedded MHC-I isotopologue calibrants
2021
Overview
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.
Publisher
National Academy of Sciences
Subject
/ Antigen Presentation - drug effects
/ Antigen Presentation - immunology
/ Antigens
/ Antigens, Neoplasm - analysis
/ Antigens, Neoplasm - drug effects
/ Antigens, Neoplasm - immunology
/ Benzimidazoles - pharmacology
/ Histocompatibility Antigens Class I - immunology
/ Histocompatibility Antigens Class I - metabolism
/ Humans
/ Major histocompatibility complex
/ MAP Kinase Kinase 1 - antagonists & inhibitors
/ Melanoma
/ Tumors
