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

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

<jats:p>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 te...

Full description

Bibliographic Details
Main Authors: Stopfer, Lauren E, Gajadhar, Aaron S, Patel, Bhavin, Gallien, Sebastien, Frederick, Dennie T, Boland, Genevieve M, Sullivan, Ryan J, White, Forest M
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Language:English
Published: Proceedings of the National Academy of Sciences 2023
Online Access:https://hdl.handle.net/1721.1/147945
Description
Summary:<jats:p>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.</jats:p>

Similar Items