MHC Class I Immunopeptidome: Past, Present, and Future

In the 35 years since the revelation that short peptides bound to major histocompatibility complex class I and II molecules are the secret of the major histocompatibility complex-restricted nature of T-cell recognition, there has been enormous progress in characterizing the immunopeptidome, the repertoire of peptide presented for immunosurveillance. Here, the major milestones in the journey are marked, the contribution of proteasomemediated splicing to the immunopeptidome is discussed, and exciting recent findings relating the immunopeptidome to the translatome revealed by ribosome profiling (RiboSeq) is detailed. Finally, what is needed for continued progress is opined about, which includes the infusion of talented young scientists into the antigen-processing field, currently undergoing a renaissance; thanks in part to the astounding success of T-cell-based cancer immunotherapy.

Automated summary

In the past 35 years, significant progress has been made in the study of immunopeptidome, revealing the importance of short peptides binding to major histocompatibility complex in T-cell recognition. This article discusses the contribution of proteasome-mediated splicing to immunopeptidome and the recent findings linking immunopeptidome to the translatome revealed by ribosome profiling. It also emphasizes the need to attract talented young scientists to further advance antigen-processing research, which has seen remarkable success in T-cell-based cancer immunotherapy.