scholarly journals SARS-CoV-2 inhibits induction of the MHC class I pathway by targeting the STAT1-IRF1-NLRC5 axis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ji-Seung Yoo ◽  
Michihito Sasaki ◽  
Steven X. Cho ◽  
Yusuke Kasuga ◽  
Baohui Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mhc Class I ◽  
Critical Role ◽  
Class I ◽  
Immune Evasion Mechanism ◽  
Antigen Presentation Pathway ◽  
Presentation Pathway ◽  
Epithelial Cell Lines ◽  
Orf6 Protein ◽  
Infected Epithelial Cell

AbstractThe MHC class I-mediated antigen presentation pathway plays a critical role in antiviral immunity. Here we show that the MHC class I pathway is targeted by SARS-CoV-2. Analysis of the gene expression profile from COVID-19 patients as well as SARS-CoV-2 infected epithelial cell lines reveals that the induction of the MHC class I pathway is inhibited by SARS-CoV-2 infection. We show that NLRC5, an MHC class I transactivator, is suppressed both transcriptionally and functionally by the SARS-CoV-2 ORF6 protein, providing a mechanistic link. SARS-CoV-2 ORF6 hampers type II interferon-mediated STAT1 signaling, resulting in diminished upregulation of NLRC5 and IRF1 gene expression. Moreover, SARS-CoV-2 ORF6 inhibits NLRC5 function via blocking karyopherin complex-dependent nuclear import of NLRC5. Collectively, our study uncovers an immune evasion mechanism of SARS-CoV-2 that targets the function of key MHC class I transcriptional regulators, STAT1-IRF1-NLRC5.

Identifying novel ubiquitin E3 ligases in the MHC class I antigen presentation pathway

2012 ◽  
Vol 51 (1) ◽  
pp. 21
Author(s):  
Paul Lehner ◽  
Florencia Cano ◽  
Marian Burr ◽  
Richard Timms ◽  
Jessica Boname ◽  
...  
Keyword(s):  
Antigen Presentation ◽  
Mhc Class I ◽  
Class I ◽  
E3 Ligases ◽  
Antigen Presentation Pathway ◽  
Presentation Pathway ◽  
Mhc Class I Antigen

scholarly journals An Evolutionarily Conserved Function of Polycomb Silences the MHC Class I Antigen Presentation Pathway and Enables Immune Evasion in Cancer

Cancer Cell ◽  
2019 ◽  
Vol 36 (4) ◽  
pp. 385-401.e8 ◽  
Author(s):  
Marian L. Burr ◽  
Christina E. Sparbier ◽  
Kah Lok Chan ◽  
Yih-Chih Chan ◽  
Ariena Kersbergen ◽  
...  
Keyword(s):  
Antigen Presentation ◽  
Mhc Class I ◽  
Immune Evasion ◽  
Class I ◽  
Antigen Presentation Pathway ◽  
Presentation Pathway ◽  
Evolutionarily Conserved ◽  
Mhc Class I Antigen

scholarly journals TAPBPR alters MHC class I peptide presentation by functioning as a peptide exchange catalyst

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Clemens Hermann ◽  
Andy van Hateren ◽  
Nico Trautwein ◽  
Andreas Neerincx ◽  
Patrick J Duriez ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Class I ◽  
Mhc I ◽  
Histocompatibility Complex ◽  
Antigen Presentation Pathway ◽  
Presentation Pathway ◽  
Peptide Presentation ◽  
Peptide Exchange ◽  
Specific Peptide

Our understanding of the antigen presentation pathway has recently been enhanced with the identification that the tapasin-related protein TAPBPR is a second major histocompatibility complex (MHC) class I-specific chaperone. We sought to determine whether, like tapasin, TAPBPR can also influence MHC class I peptide selection by functioning as a peptide exchange catalyst. We show that TAPBPR can catalyse the dissociation of peptides from peptide-MHC I complexes, enhance the loading of peptide-receptive MHC I molecules, and discriminate between peptides based on affinity in vitro. In cells, the depletion of TAPBPR increased the diversity of peptides presented on MHC I molecules, suggesting that TAPBPR is involved in restricting peptide presentation. Our results suggest TAPBPR binds to MHC I in a peptide-receptive state and, like tapasin, works to enhance peptide optimisation. It is now clear there are two MHC class I specific peptide editors, tapasin and TAPBPR, intimately involved in controlling peptide presentation to the immune system.

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