The DRiP hypothesis decennial: support, controversy, refinement and extension

In 1996, to explain the rapid presentation of viral proteins to CD8+ T cells, it was proposed that peptides presented by MHC class I molecules derive from defective ribosomal products (DRiPs), presumed to be polypeptides arising from in-frame translation that fail to achieve native structure owing to inevitable imperfections in transcription, translation, post-translational modifications or protein folding. Here, we consider findings that address the DRiP hypothesis, and extend the hypothesis by proposing that cells possess specialized machinery, possibly in the form of ‘immunoribosomes’, to couple protein synthesis to antigen presentation.