Absolute quantification of tumor antigens using embedded MHC-I isotopologue calibrants.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34497125.
- Also identified by DOI 10.1073/pnas.2111173118 and PMC identifier 8449407.
- Licence recorded as CC BY-NC-ND.
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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.
Medical subject headings
- Antigen Presentation
- Antigens, Neoplasm
- Benzimidazoles
- Histocompatibility Antigens Class I
- MAP Kinase Kinase 1
- Melanoma