Post-translational splicing is a fascinating process in its own right, ™ says Dr. Beno?®t Van den Eynde, the senior author of the study, but it also has important implications for the design of cancer or HIV vaccines based on peptide antigens. Synthetic peptides being investigated in early-phase clinical trials of vaccines are usually designed based on the gene sequence of cancer-specific proteins. However post-translational splicing may be modifying the peptide antigens in ways that we haven ™t even suspected before now.

The issue of predicted versus post-translationally spliced, novel peptide antigens is a particularly important consideration when monitoring immunological responses to cancer vaccines in patients. The existing methodologies typically quantify the presence of T cells specific for the predicted peptide antigen, and would not detect T cells specific for the novel peptide antigen. Additional studies are required to determine if proteome-mediated post-translational splicing occurs in relation to cancer and/or virally-infected cells, and if so, the frequency of occurrence of such novel peptide antigens in these diseases.

The discovery of post-translational splicing has immunologists intrigued by the additional complications in antigen identification, and cell biologists excited by a new insight into the proteasome ™s bag of tricks. However for geneticists and biochemists, the discovery of post-translational splicing may have produced a slight sense of unease. Until we know exactly when, why, and how often post-translational splicing occurs, we can no longer automatically assume that the human genome holds all the answers for predicting protein sequences.