Abstract
Viruses are known to employ different strategies to manipulate the major histocompatibility (MHC) class I antigen presentation pathway to avoid recognition of the infected host cell by the immune system. However, viral control of antigen presentation via the processes that supply and select antigenic peptide precursors is yet relatively unknown. The Epstein-Barr virus (EBV)-encoded EBNA1 is expressed in all EBV-infected cells, but the immune system fails to detect and destroy EBV-carrying host cells. This immune evasion has been attributed to the capacity of a Gly-Ala repeat (GAr) within EBNA1 to inhibit MHC class I restricted antigen presentation. Here we demonstrate that suppression of mRNA translation initiation by the GAr in cis is sufficient and necessary to prevent presentation of antigenic peptides from mRNAs to which it is fused. Furthermore, we demonstrate a direct correlation between the rate of translation initiation and MHC class I antigen presentation from a certain mRNA. These results support the idea that mRNAs, and not the encoded full length proteins, are used for MHC class I restricted immune surveillance. This offers an additional view on the role of virus-mediated control of mRNA translation initiation and of the mechanisms that control MHC class I restricted antigen presentation in general.
Highlights
Presentation of antigenic peptides on major histocompatibility (MHC) class I molecules is a signal for CD8+ T cells to distinguish between cells that express self or non-self antigens and forms an important part of the immune system’s capacity to fight parasite invasion
This allowed us to monitor any effect the Gly-Ala repeat (GAr) has on antigen presentation from these mRNAs using the B3Z CD8+ T hybridoma that is specific for the SL8 in the context of H-2Kb MHC class I molecules [23]
Our results further underline the notion that the capacity of EBNA1 to evade the MHC class I antigen presentation pathway and the detection by CD8+ T cells relies on the Glycine-Alanine repeat (GAr) sequence [15,16,20,35]
Summary
Presentation of antigenic peptides on major histocompatibility (MHC) class I molecules is a signal for CD8+ T cells to distinguish between cells that express self or non-self antigens and forms an important part of the immune system’s capacity to fight parasite invasion. To explain the rapidity of viral-antigen presentation, a model has been proposed in which a fraction of rapidly degraded mRNA translation products (RDPs) [8] or defective ribosomal products (DRiPs) [9] with a half-life of less than 10 minutes constitute the main source for antigenic peptides. This model has been supported by the rapid slow down of TAP system by blocking protein synthesis and the equal rapid suppression of antigen presentation when transcription of an mRNA encoding a protein with a long half life is shut off [10]. The translation mechanisms that govern the synthesis of antigenic peptide products are unknown
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
