Game of Omes: ribosome profiling expands the MHC-I immunopeptidome

Peptide ligands presented by cell-surface MHC class-I molecules enable T cells to eradicate intracellular pathogens and cancers. The presented peptide repertoire, the class-I immunopeptidome, is generated from each cell's translatome in a highly biased manner to avoid overrepresenting highly abundant translation products. The immunopeptidome can only be defined by mass spectrometry (MS). Here, we review recent advances in immunopeptidomics, focusing on using ribosome profiling as the optimal MS database to optimize the false- and failed-discovery rates and relate these findings to the contribution of defective ribosomal products and cellular quality control mechanisms to MHC class-I antigen processing and presentation.