Proteomics

Dataset Information

213

Integrative MHC-I peptidome quantitation with isobaric tagging mass spectrometry


ABSTRACT: Despite the appreciation of CD8+ T cell anti-tumor immune responses towards improvement patient outcomes, the MHC-I peptides that facilitate the response are poorly described. Alternatively, whether cancer therapies alter the MHC-I peptide repertoire has not been fully assessed due to the lack of quantitative strategies. In this regard, anthracyclines and ionizing radiation both increase the infiltration of CD8+ T cells into tumors but whether they do so by altering the MHC-I peptidome repertoire is not known. To investigate this, we developed a platform for screening therapy-induced MHC-I peptides by quantitative, multiplexed measurement of MHC-I peptides with tandem mass tags (TMT). We show that both ionizing radiation and the anthracycline doxorubicin induce MHC-I peptides that are largely derived from mitotic progression and cell cycle proteins. Our approach enables further strategies to understand how small molecules and other therapies alter MHC-I peptide presentation that may be harnessed for CD8+ T cell-based immunotherapies.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo sapiens  

TISSUE(S): Cell Suspension Culture

DISEASE(S): Colon Cancer

SUBMITTER: Patrick Murphy  

LAB HEAD: Shashi Gujar

PROVIDER: PXD011464 | Pride | 2019-03-05

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
286535_m12743Swissprot_all.mzid.gz Mzid
286536_m12744Swissprot_all.mzid.gz Mzid
286537_m12745Swissprot_all.mzid.gz Mzid
286538_m12746Swissprot_all.mzid.gz Mzid
286539_m12747Swissprot_all.mzid.gz Mzid
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Publications

Multiplexed Relative Quantitation with Isobaric Tagging Mass Spectrometry Reveals Class I Major Histocompatibility Complex Ligand Dynamics in Response to Doxorubicin.

Murphy J Patrick JP   Yu Qijia Q   Konda Prathyusha P   Paulo Joao A JA   Jedrychowski Mark P MP   Kowalewski Daniel J DJ   Schuster Heiko H   Kim Youra Y   Clements Derek D   Jain Aditya A   Stevanovic Stefan S   Gygi Steven P SP   Mancias Joseph D JD   Gujar Shashi S  

Analytical chemistry 20190222 8


MHC-I peptides are intracellular-cleaved peptides, usually 8-11 amino acids in length, which are presented on the cell surface and facilitate CD8<sup>+</sup> T cell responses. Despite the appreciation of CD8<sup>+</sup> T-cell antitumor immune responses toward improvement in patient outcomes, the MHC-I peptide ligands that facilitate the response are poorly described. Along these same lines, although many therapies have been recognized for their ability to reinvigorate antitumor CD8<sup>+</sup>  ...[more]

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