Novel biochemistry: post-translational protein splicing and other lessons from the school of antigen processing.
In the past 15 years, the molecular identification of antigens that can mediate the killing of tumor cells by T cells has been vigorously pursued. Molecular identification of tumor-associated antigens not only provided the means to activate or monitor anti-tumor immunity, but also gave insights into new and unexpected biochemical processes that are taking place within cells. Post-translational splicing, a phenomenon previously identified only in lower organisms or plants, has recently been added to the list of atypical processes generating proteins in humans. The proteasome, whose main function is to degrade intracellular proteins, appears to catalyze this splicing reaction. The discovery of post-translational splicing has immediate and important implications for the complexity of the major histocompatibility complex (MHC) class I peptide repertoire and for the immune recognition of self- and foreign peptides.