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Self-Inhibition of Synthesis and Antigen Presentation by Epstein 和爱泼斯坦自我抑制抗原呈递的合成
Self-Inhibition of Synthesis and Antigen Presentation by Epstein-Barr Virus-Encoded EBNA1: An Explanation Y. Yin, B. Manoury, R. Fahraeus First: A Little About MHC-1 Major Histocompatibility Complex-1 presents viral peptides to CD8+ cytotoxic T cells (CTL in this paper). Interacts with CD8a, T cell Receptor (TCR) on T Cell A Little About MHC-1: MHC-1 found on all cells in all tissues If it can be infected, it will produce MHC-1. Some tissues present more immune system cells Some present less hepatocytes Some almost none erythrocytes: no nucleus = no viral replication ? inefficient to have MHC-1 A Little About MHC-1: Structure Two polypeptide chains a chain: large, three domains Spans membrane a1 and a2 form walls of cleft on surface of molecule b2 Microglobulin: small, immunoglobulin-like domain MHC-1 binds short peptides of 8-10 a.a. in length Ends of peptide bind to groove Can also bind peptides at anchor residues polymorphisms A Little About MHC-1: Peptide Processing In ER: MHC-1a stabilized by calnexin b2m then binds; a:b2m binds to chaperones, TAP via tapasin. In cytosol: Proteasome digests cytosolic proteins TAP channel delivers small peptides to MHC MHC exported to outer membrane And Now the Paper: Question: how does GAr work to prevent EBNA1 antigen presentation by MHC-1? Basics: What is known: GAr of EBNA1 inhibits antigen presentation on MHC-1 Original Hypothesis: GAr was first thought to inhibit proteasome degradation ? no peptide to be presented on MHC-1 New Hypothesis: Coupled with the above, GAr also inhibits mRNA translation of EBNA1 ? less protein to be digested by proteasome, presented by MHC-1 Old Hypothesis: Original Hypothesis: GAr was first thought to inhibit proteasome degradation ? no peptide to be presented on MHC-1 Observed: Cells fail to present antigen on MHC-1 when GAr is present on transcript Fusion of GAr to other protein prevents antigen presentation of fused protein GAr increases half-life of EBNA1 by inhibiting degradati
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