Repertoire of Classical MHC Class I and Class II Molecules

The mammalian immune system has evolved to respond to pathogenic, environmental, and cellular changes in order to maintain the health of the host. These responses include the comparatively primitive innate immune response, which represents a rapid and relatively nonspecific reaction to challenge by pathogens and the more complex cellular adaptive immune response. This adaptive response evolves with the pathogenic challenge, involves the cross talk of several cell types and is highly specific to the pathogen due to the liberation of peptide antigens and their presentation on the surface of affected cells. Together these two forms of immunity provide a surveillance mechanism for the system wide scrutiny of cellular function, environment, and health. The recognition of peptide antigens in the context of host MHC is key to understanding immunity to infectious disease, autoimmune disease, cancer, and allergies. It also underpins most vaccination and immunotherapeutic strategies. This article therefore describes how the peptide repertoire of MHC molecules (the immunopeptidome) is determined, how this information can be used in the context of highly polymorphic and personalized immunogenetics and recent developments in our understanding of the breadth and variability of the immunopeptidome.