Immunoproteomics: mass spectrometry-based methods to study the targets of the immune response

The mammalian immune system has evolved to display fragments of protein antigens derived from microbial pathogens to immune effector cells. These fragments are typically peptides liberated from the intact antigens through distinct proteolytic mechanisms that are subse-quently transported to the cell surface bound to chaper-one-like receptors known as major histocompatibility complex (MHC) molecules. These complexes are then scrutinized by effector T cells that express clonally dis-tributed T cell receptors with specificity for specific MHC-peptide complexes. In normal uninfected cells, this proc-ess of antigen processing and presentation occurs continuously, with the resultant array of self-antigen-de-rived peptides displayed on the surface of these cells. Changes in this peptide landscape of cells act to alert immune effector cells to changes in the intracellular en-vironment that may be associated with infection, malig-nant transformation, or other abnormal cellular pro-cesses, resulting in a cascade of events that result in their elimination. Because peptides play such a crucial role in informing the immune system of infection with viral or microbial pathogens and the transformation of cells in malignancy, the tools of proteomics, in particular mass spectrometry, are ideally suited to study these immune responses at a molecular level. Here we review recent advances in the studies of immune responses that have utilized mass spectrometry and associated technologies, with specific examples from collaboration between ou