Cellular Mechanisms that Edit the Immunopeptidome

The adaptive immune response relies on the ability of T-lymphocytes to recognize small antigenic peptides presented on the cell surface by specialized receptors of the Major Histocompatibility Complex (MHC). These peptides are either generated by the degradation of intracellular proteins (MHC class I pathway) or by the degradation of internalized extracellular proteins (MHC class II pathway and cross-presentation pathway). The number of proteins that can be degraded by these pathways runs to the thousands leading to a staggering number of possible peptide fragments. A small subset of these peptides is selected by the cell's processing and presentation mechanisms to be presented on the cell surface by MHC molecules and has been defined as the immunopeptidome. The peptide sequences that comprise the immunopeptidome control the immune response and variations of this peptide repertoire are key to understanding the host's ability to fight pathogens, immune response to cancer as well as predisposition to autoimmunity and allergies. In the last few years it has been established that the composition of the immunopeptidome is regulated by specific cellular mechanisms that influence qualitative and quantitative aspects of the cellular immune response in a process that has been described as antigenic peptide editing. This review explores the current knowledge on these cellular mechanisms and discusses the parallels between editing the MHC class I and class II immunopeptidomes.