Differential arginine methylation of the G-protein pathway suppressor GPS-2 recognized by tumor-specific T cells in melanoma

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Saulius JarmalaviciusPeter Walden

Abstract

The aim of the study was to identify as potential therapeutic targets specific molecular alterations in tumor cells recognized by the immune system. To identify such targets, we analyzed the human leukocyte antigen (HLA) peptidomes of human melanoma cells by 2-dimensional nano-HPLC/mass spectrometry and tested the immunological significance of the peptides by ex vivo ELISpot assays with lymphocytes from melanoma patients. The peptide SQNPRFYHK was identified as derived from the regulator of the nuclear corepressor complex (NCoR) G-protein pathway suppressor 2 (GPS-2) and to be differentially unmethylated, monomethylated or asymmetrically dimethylated at the arginine. The methylation state was specifically recognized by the immune system in that only the monomethylated variant induced T-cell responses and significantly stronger responses in patients than in healthy controls. The methylations were confirmed with synthetic analogues and in vitro radiolabeling assays with recombinant GPS-2 and synthetic peptides. The immunity of the 3 variants of GPS-2 was tested in T-cell assays with T lymphocytes of melanoma patients compared with healthy donors. The results show for the first time that GPS-2 is differentially methylated at a sit...Continue Reading

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Citations

Aug 8, 2012·The Journal of Biological Chemistry·Saulius JarmalaviciusPeter Walden
Aug 10, 2016·Journal of Proteome Research·Fabio MarinoAlbert J R Heck
Aug 7, 2018·Expert Review of Proteomics·Sri H RamarathinamAnthony W Purcell
Jul 12, 2019·Frontiers in Endocrinology·Ning LiangEckardt Treuter
Feb 11, 2011·Current Opinion in Oncology

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