Prof. Jonathan Yewdell is a distinguished immunologist and virologist whose research has transformed understanding of how the immune system recognizes virus-infected cells. Trained at Princeton University, the University of Pennsylvania, and the Wistar Institute, he built an interdisciplinary foundation in viral immunology, monoclonal antibodies, and cell biology. He made important early contributions to immunodominance and antigen processing before joining the National Institutes of Health (NIH) in 1987. His laboratory made major discoveries in influenza virus biology, including new viral gene products, semi-infectious virions, and mechanisms of antigenic drift. He also helped define key principles of class I antigen processing, peptide loading, amino-terminal trimming, and the DRiP origin of viral peptides. Beyond immunology, his work has advanced understanding of protein synthesis, protein degradation, retrograde transport, and stress-induced recoding. His current research focuses on influenza A virus evolution, translation-related questions in viral and cancer immunology, and immunodominance in antibody responses to viruses. He has been an outspoken advocate for improving biomedical training and research culture, and has supported younger scientists through freely accessible career guidance.

How MHC I Peptides Are Generated for Viral and Cancer Immunosurveillance

The talk focuses on peptide generation from DRiPs (defective ribosomal products), ribosomal generated polypeptides that don’t achieve folded stable forms and are proteolytically converted into peptides presented by MHC I molecules for CD8+ T cell immunosurveillance. Influenza A virus DRiPs will occupy center stage. I will discuss dozens of novel influenza virus gene products we discovered in characterizing DRiPs. These include PB1-F2, the granddaddy of flu alternative reading frame proteins, UFOs generated from host mRNA start codons, and most recently, numerous open reading frames encoded by the negative strand. The talk will conclude with a brief discussion of DRiPs and cancer, and the contribution of “immunoribosomes” (subsets of ribosomes) to the cancer immuopeptidome.