The DRiP hypothesis decennial: support, controversy, refinement and extension

Yewdell, Jonathan W.; Nicchitta, Christopher V.

doi:10.1016/j.it.2006.06.008

Cited by 199 publications

(191 citation statements)

References 47 publications

Supporting

Mentioning

179

Contrasting

Unclassified

Order By: Relevance

“…These observations are important for antigen presentation as studies from our group and others show that the translational efficiency of viral proteins directly affects the generation of rapidly degrading polypeptides (RDPs), which are the primary source of CD8 + T-cell epitopes 7,9,14,15,18,[37][38][39][40][41][42][43][44] . EBNA1 is an ideal model to demonstrate that CD8 + T-cell epitopes are less efficiently processed from a poorly synthesized wild-type EBNA1 generating fewer RDPs compared with a more efficiently synthesized codon-modified EBNA1 where Gquadruplex structures have been destabilized, with a resultant increase in RDPs.…”

Section: Discussionmentioning

confidence: 99%

G-quadruplexes regulate Epstein-Barr virus–encoded nuclear antigen 1 mRNA translation

et al. 2014

View full text Add to dashboard Cite

Viruses that establish latent infections have evolved unique mechanisms to avoid host immune recognition. Maintenance proteins of these viruses regulate their synthesis to levels sufficient for maintaining persistent infection but below threshold levels for host immune detection. The mechanisms governing this finely tuned regulation of viral latency are unknown. Here we show that mRNAs encoding gammaherpesviral maintenance proteins contain within their open reading frames clusters of unusual structural elements, G-quadruplexes, which are responsible for the cisacting regulation of viral mRNA translation. By studying the Epstein-Barr virus-encoded nuclear antigen 1 (EBNA1) mRNA, we demonstrate that destabilization of G-quadruplexes using antisense oligonucleotides increases EBNA1 mRNA translation. In contrast, pretreatment with a G-quadruplex-stabilizing small molecule, pyridostatin, decreases EBNA1 synthesis, highlighting the importance of G-quadruplexes within virally encoded transcripts as unique regulatory signals

show abstract

Section: Discussionmentioning

confidence: 99%

G-quadruplexes regulate Epstein-Barr virus–encoded nuclear antigen 1 mRNA translation

et al. 2014

View full text Add to dashboard Cite

show abstract

“…This raises the question whether DRiPs and DRiP-derived peptides are simple by-products of protein synthesis or if cells have evolved mechanisms regulating DRiP formation and/or processing. Yewdell and Nicchitta (2006) suggested the existence of "immunoribosomes" specialized on the production of substrates for the MHC class I restricted antigen processing pathway (Yewdell and Nicchitta, 2006). Such immunoribosomes may have a different subunit composition or localize in a different intracellular compartment than conventional ribosomes.…”

Section: Discussionmentioning

confidence: 99%

Chaperone BAG6 is dispensable for MHC class I antigen processing and presentation

Bitzer

Basler

Groettrup

2016

Molecular Immunology

View full text Add to dashboard Cite

a b s t r a c tAntigen processing for direct presentation on MHC class I molecules is a multistep process requiring the concerted activity of several cellular complexes. The essential steps at the beginning of this pathway, namely protein synthesis at the ribosome and degradation via the proteasome, have been known for years. Nevertheless, there is a considerable lack of factors identified to function between protein synthesis and degradation during antigen processing. Here, we analyzed the impact of the chaperone BAG6 on MHC class I cell surface expression and presentation of virus-derived peptides. Although an essential role of BAG6 in antigen processing has been proposed previously, we found BAG6 to be dispensable in this pathway. Still, interaction of BAG6 and the model antigen tyrosinase was enhanced during proteasome inhibition pointing towards a role of BAG6 in antigen degradation. Redundant chaperone pathways potentially mask the contribution of BAG6 to antigen processing and presentation.

show abstract

“…During infection, viral peptides are produced in the cytosol by the proteasomal destruction of predominantly defective translation products (11). These peptides are then imported into the endoplasmic reticulum (ER) by the dedicated peptide transporter TAP and trimmed to 8-to 9-mers by the ER-associated protease (ERAP) (12,13).…”

mentioning

confidence: 99%

Cowpox Virus Evades CTL Recognition and Inhibits the Intracellular Transport of MHC Class I Molecules

Dasgupta

Hammarlund

Slifka

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

Orthopoxviruses evade host immune responses by using a number of strategies, including decoy chemokine receptors, regulation of apoptosis, and evasion of complement-mediated lysis. Different from other poxviral subfamilies, however, orthopoxviruses are not known to evade recognition by CTL. In fact, vaccinia virus (VV) is used as a vaccine against smallpox and a vector for eliciting strong T cell responses to foreign Ags. and both human and mouse T cells are readily stimulated by VV-infected APC in vitro. Surprisingly, however, CD8+ T cells of mice infected with cowpox virus (CPV) or VV recognized APC infected with VV but not APC infected with CPV. Likewise, CD8+ T cells from vaccinated human subjects could not be activated by CPV-infected targets and CPV prevented the recognition of VV-infected APC upon coinfection. Because CD8+ T cells recognize viral peptides presented by MHC class I (MHC I), we examined surface expression, total levels, and intracellular maturation of MHC I in CPV- and VV-infected human and mouse cells. Although total levels of MHC I were unchanged, CPV reduced surface levels and inhibited the intracellular transport of MHC I early during infection. CPV did not prevent peptide loading of MHC I but completely inhibited MHC I exit from the endoplasmic reticulum. Because this inhibition was independent of viral replication, we conclude that an early gene product of CPV abrogates MHC I trafficking, thus rendering CPV-infected cells “invisible” to T cells. The absence of this immune evasion mechanism in VV likely limits virulence without compromising immunogenicity.

show abstract

The DRiP hypothesis decennial: support, controversy, refinement and extension

Cited by 199 publications

References 47 publications

G-quadruplexes regulate Epstein-Barr virus–encoded nuclear antigen 1 mRNA translation

G-quadruplexes regulate Epstein-Barr virus–encoded nuclear antigen 1 mRNA translation

Chaperone BAG6 is dispensable for MHC class I antigen processing and presentation

Cowpox Virus Evades CTL Recognition and Inhibits the Intracellular Transport of MHC Class I Molecules

Contact Info

Product

Resources

About