Investigating the role of defective ribosomal products in influenza induced immune responses

CD8+ T cells eliminate virus infected cells by recognizing small portions of viral proteins, known as peptides, displayed by surface MHC class I molecules. The source of these important peptides remains highly controversial as the rapid presentation of viral peptides often contrasts starkly with the high stability of their source proteins. This has led to the DRiPs (Defective Ribosomal Products) hypothesis of antigen presentation, which posits that errors in transcription, translation and post-translational protein maturation result in synthesis of rapidly degraded peptides that are exploited for immunosurveillance. In particular, although the contribution of translational errors to viral peptide generation has been determined in model systems, the relative contributions of mis-translation to the induction of natural anti-viral TCD8+ responses is still uncertain.

We aim to identify and quantitate the relative contributions of DRiPs-generated peptides to the protective anti-influenza immune response in mice and humans. Our findings have the potential to greatly change the way we identify novel anti-pathogen immune responses, especially for future vaccine development.

External collaborators: Jonathan W. Yewdell and Jack R. Bennink, NIH