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Quantitative phosphoproteomic analysis reveals involvement of PD-1 in multiple T cell functions

ABSTRACT: The programmed cell death protein 1 (PD-1) pathway is a critical inhibitory checkpoint for T cells, and antibodies blocking PD-1 promote immune-mediated identification and clearance of malignant cells. Despite the success of these antibodies, the majority of patients do not respond to PD-1 blockade and many experience immune-related adverse events. As such, there is an urgent need to better understand PD-1 signaling, not just in order to explain the mechanism behind the unfavorable responses, but also to develop next-generation therapeutics. We performed global quantitative phosphoproteomic interrogation of PD-1 signaling in human T cells and by complementing our analysis with functional validation assays in primary human cells. To investigate the T cell phosphoproteome, Jurkat cells were treated with either a) anti human CD3 antibody, b) anti human CD3 antibody together with recombinant human PD-L2-Fc or c) IgG1 isotype control antibody for 30 seconds, 5 minutes or 15 minutes. The global and phosphoproteome was quantified using an isobaric labeling approach (e.g. TMT) in combination with TiO2 enrichment and three different pY specific antibodies.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Beatrix Ueberheide

PROVIDER: MSV000084813 | MassIVE | Thu Jan 16 13:33:00 GMT 2020

REPOSITORIES: MassIVE

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