The Synthesis of Truncated Polypeptides for Immune Surveillance and Viral Evasion |
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Authors: | Sylvain Cardinaud Shelley R Starck Piyanka Chandra Nilabh Shastri |
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Institution: | Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, California, United States of America.;University of California San Francisco, United States of America |
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Abstract: | BackgroundCytotoxic T cells detect intracellular pathogens by surveying peptide loaded MHC class I molecules (pMHC I) on the cell surface. Effective immune surveillance also requires infected cells to present pMHC I promptly before viral progeny can escape. Rapid pMHC I presentation apparently occurs because infected cells can synthesize and present peptides from antigenic precursors called defective ribosomal products (DRiPs). The molecular characteristics of DRiPs are not known.Methodology/Principal FindingsHere, using a novel method for detecting antigenic precursors and proteolytic intermediates, we tracked the synthesis and processing of Epstein-Barr Virus encoded nuclear antigen 1 (EBNA1). We find that ribosomes initiated translation appropriately, but rapidly produced DRiPs representing ∼120 amino acid truncated EBNA1 polypeptides by premature termination. Moreover, specific sequences in EBNA1 mRNA strongly inhibited the generation of truncated DRiPs and pMHC I presentation.SignificanceOur results reveal the first characterization of virus DRiPs as truncated translation products. Furthermore, production of EBNA1-derived DRiPs is down-regulated in cells, possibly limiting the antigenicity of EBNA1. |
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