Proteomics

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CT26 Proteome and Immunopeptidome treated with Ionizing Radiation


ABSTRACT: This project explored the relationship between ionizing radiation and antigen presentation using both proteomic and immunopeptidomics methodologies. We investigated the radiation-specific changes which occur in the colorectal tumor cell proteome associated with changes in dose and time after irradiation. We used this data to observe the changes in key regulators and effector proteins of the antigen processing and presentation machinery. Furthermore, a parallel immunopeptidomics analysis enabled a peptide-level assessment of antigen presentation to correlate changes observed in the proteome thereby defining a radiation-specific peptide repertoire. A nuanced relationship between protein expression and antigen presentation was observed where radiation-induced changes in proteins do not always correlate with increased presentation of associated peptides. Furthermore, a neoantigen which increases in the context of radiation was characterised. This study provides new insights into how radiation enhances antigen processing and presentation that could be suitable for the development of combinatorial therapies.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Colon Cancer

SUBMITTER: Arun Tailor  

LAB HEAD: Nicola Ternette

PROVIDER: PXD032003 | Pride | 2022-10-04

REPOSITORIES: Pride

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Publications

Ionizing Radiation Drives Key Regulators of Antigen Presentation and a Global Expansion of the Immunopeptidome.

Tailor Arun A   Estephan Hala H   Parker Robert R   Woodhouse Isaac I   Abdulghani Majd M   Nicastri Annalisa A   Jones Keaton K   Salatino Silvia S   Muschel Ruth R   Humphrey Timothy T   Giaccia Amato A   Ternette Nicola N  

Molecular & cellular proteomics : MCP 20220909 11


Little is known about the pathways regulating MHC antigen presentation and the identity of treatment-specific T cell antigens induced by ionizing radiation. For this reason, we investigated the radiation-specific changes in the colorectal tumor cell proteome. We found an increase in DDX58 and ZBP1 protein expression, two nucleic acid sensing molecules likely involved in induction of the dominant interferon response signature observed after genotoxic insult. We further observed treatment-induced  ...[more]

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