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

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...

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Detalles Bibliográficos
Autores principales: Stopfer, Lauren E., Gajadhar, Aaron S., Patel, Bhavin, Gallien, Sebastien, Frederick, Dennie T., Boland, Genevieve M., Sullivan, Ryan J., White, Forest M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2021
Materias:
Biological Sciences
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449407/
https://www.ncbi.nlm.nih.gov/pubmed/34497125
http://dx.doi.org/10.1073/pnas.2111173118
Descripción
Sumario: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.

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