The synthesis of truncated polypeptides for immune surveillance and viral evasion.
BACKGROUND
Cytotoxic 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.


RESULTS
Here, 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 approximately 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.


CONCLUSIONS
Our 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.
Cardinaud
Sylvain
S
Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, California, United States of America.
Starck
Shelley R
SR
Chandra
Piyanka
P
Shastri
Nilabh
N
D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D057131:Immune Evasion; D012333:RNA, Messenger / Q000235:genetics; D012269:Ribosomal Proteins / Q000737:chemistry / Q000276:immunology*; D014764:Viral Proteins / Q000737:chemistry / Q000276:immunology*
D017931:DNA Primers; D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger; D012269:Ribosomal Proteins; D014764:Viral Proteins