Identification of Natural MHC Class II Presented Phosphopeptides and Tumor-Derived MHC Class I Phospholigands

MHC molecules present protein-derived peptides to T lymphocytes. By developing TiO₂-based microcentrifugation columns, we identified the first phosphorylated MHC class I ligands from tumor tissue (renal cell carcinoma) and, by comparison to healthy renal tissue, found one Brf1-derived ligand as potentially tumor-associated. We further discovered the first natural phosphorylated MHC class II ligands. They revealed several novel phosphorylation sites of significant transmembrane receptors, such as Frizzled 6, CXCR4 and CD20.