Ribosomal frameshifting and transcriptional slippage: From genetic steganography and cryptography to adventitious use

Atkins, John F.; Loughran, Gary; Bhatt, Pramod R.; Firth, Andrew E.; Baranov, Pavel V.

Major Histocompatibility Complex (MHC) class I molecules bind and present oligopeptides at the cell surface. This presentation of peptides enables lymphocytemediated immunosurveillance important for viral and tumor immunity. It is upregulated by interferons and certain other cytokines. In addition to peptides being derived from mature 'retiree' proteins, a proportion of the peptides come from proteins being synthesized, or directly afterward. Part of the initial reason for appreciating this came from the rapid time after viral infection that infected cells display viral antigens recognized by specific CD8+ cytotoxic T-lymphocytes, with viral counter-attack being relevant (701) . This led to the DRiP (Defective Ribosomal Products) hypothesis (702) which was later broadened to include products derived from ribosomal frameshifting (703, 704) , transcriptional indels (705), various other non-standard events and notably potential specialized ribosomes 'immuno-ribosomes' (706) . Detection is highly sensitive and antibiotic treatment can affect such peptide display (707) . There are numerous fascinating and important unanswered questions about the origin of peptides selected for display, and the extent of relevance of cotranslational protein degradation (708) and of frameshifting are only a couple of the unknowns.