Structural aspects of chemical modifications in the MHC-restricted immunopeptidome; Implications for immune recognition

Significant advances in mass-spectroscopy (MS) have made it possible to investigate the cellular immunopeptidome, a large collection of MHC-associated epitopes presented on the surface of healthy, stressed and infected cells. These approaches have hitherto allowed the unambiguous identification of large cohorts of epitope sequences that are restricted to specific MHC class I and II molecules, enhancing our understanding of the quantities, qualities and origins of these peptide populations. Most importantly these analyses provide essential information about the immunopeptidome in responses to pathogens, autoimmunity and cancer, and will hopefully allow for future tailored individual therapies. Protein post-translational modifications (PTM) play a key role in cellular functions, and are essential for both maintaining cellular homeostasis and increasing the diversity of the proteome. A significant proportion of proteins is post-translationally modified, and thus a deeper understanding of the importance of PTM epitopes in immunopeptidomes is essential for a thorough and stringent understanding of these peptide populations. The aim of the present review is to provide a structural insight into the impact of PTM peptides on stability of MHC/peptide complexes, and how these may alter/modulate immune responses.