MHC-bound antigens and proteomics for novel target discovery

The MHC molecules present normal as well as disease-related and pathogen-derived peptides to T cells as a way of alerting the immune system of the health status of a cell. Proteomic technologies involving immunoaffinity purification are now extensively used to separate MHC complexes from their peptide cargo, and then the peptides are sequenced by tandem mass spectrometry. The identified peptides are tested as vaccine candidates for viral diseases, immunostimulants for treating cancer, and immune-tolerance-inducing agents for autoimmune disorders. One of the challenges in devising novel HLA-peptide-based immunotherapies is to decipher whether a therapeutic window exists between the induction of tumor immunity and the onset of autoimmunity, which can have dangerous sequelae. This review will cover these topics with an overview of the vast possibilities emerging in the field of proteomic analyses of MHC-bound antigens as novel targets for immunotherapy.