RNA editing derived epitopes function as cancer antigens to elicit immune responses

In addition to genomic mutations, RNA editingis another major mechanism creating sequence variations in proteins by introducing nucleotide changes in mRNA sequences. Deregulated RNA editingcontributes to different types of human diseases, including cancers. Here we report that peptides generated as a consequence of RNA editingare indeed naturally presented by human leukocyte antigen(HLA) molecules. We provide evidence that effector CD8+ T cells specific for edited peptides derived from cyclin I are present in human tumours and attack tumour cells that are presenting these epitopes. We show that subpopulations of cancer patients have increased peptide levels and that levels of edited RNA correlate with peptide copy numbers. These findings demonstrate that RNA editingextends the classes of HLA presented self-antigens and that these antigens can be recognised by the immune system.