Viral Proteins Interfering with Antigen Presentation Target the Major Histocompatibility Complex Class I Peptide-Loading Complex

Røder, Gustav; Geironson, Linda; Bressendorff, Iain; Paulsson, Kajsa

doi:10.1128/jvi.00207-08

Cited by 24 publications

(12 citation statements)

References 85 publications

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“…Many viruses evolved mechanisms to downregulate MHC-I to evade cytotoxic CD8 T cells (25,67). As this viral activity may make such cells more susceptible to NK cells, many viruses express in addition immunoevasins that target NK cells (26,27).…”

Section: Discussionmentioning

confidence: 99%

“…Coprecipitation depends on a number of factors, and as E3/19K may inhibit transport of HLA-I alleles with low affinity to E3/19K indirectly by binding to TAP, thereby impairing the recruitment of HLA-tapasin complexes to TAP and peptide loading (36,67), coprecipitation alone may not be a reliable measure for E3/19K activity. Thus, a lack of coprecipitation does not necessarily indicate a lack of transport inhibition [(68); H.-G. Burgert, unpublished observation].…”

Section: Second Criterion For E3/19k Function: Influence Of Mutationsmentioning

confidence: 99%

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Conserved Amino Acids within the Adenovirus 2 E3/19K Protein Differentially Affect Downregulation of MHC Class I and MICA/B Proteins

Sester

Koebernick

Owen

et al. 2009

The Journal of Immunology

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Successful establishment and persistence of adenovirus (Ad) infections are facilitated by immunosubversive functions encoded in the early transcription unit 3 (E3). The E3/19K protein has a dual role, preventing cell surface transport of MHC class I/HLA class I (MHC-I/HLA-I) Ags and the MHC-I–like molecules (MHC-I chain-related chain A and B [MICA/B]), thereby inhibiting both recognition by CD8 T cells and NK cells. Although some crucial functional elements in E3/19K have been identified, a systematic analysis of the functional importance of individual amino acids is missing. We now have substituted alanine for each of 21 aas in the luminal domain of Ad2 E3/19K conserved among Ads and investigated the effects on HLA-I downregulation by coimmunoprecipitation, pulse-chase analysis, and/or flow cytometry. Potential structural alterations were monitored using conformation-dependent E3/19K-specific mAbs. The results revealed that only a small number of mutations abrogated HLA-I complex formation (e.g., substitutions W52, M87, and W96). Mutants M87 and W96 were particularly interesting as they exhibited only minimal structural changes suggesting that these amino acids make direct contacts with HLA-I. The considerable number of substitutions with little functional defects implied that E3/19K may have additional cellular target molecules. Indeed, when assessing MICA/B cell-surface expression we found that mutation of T14 and M82 selectively compromised MICA/B downregulation with essentially no effect on HLA-I modulation. In general, downregulation of HLA-I was more severely affected than that of MICA/B; for example, substitutions W52, M87, and W96 essentially abrogated HLA-I modulation while largely retaining the ability to sequester MICA/B. Thus, distinct conserved amino acids seem preferentially important for a particular functional activity of E3/19K.

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Section: Discussionmentioning

confidence: 99%

Section: Second Criterion For E3/19k Function: Influence Of Mutationsmentioning

confidence: 99%

Conserved Amino Acids within the Adenovirus 2 E3/19K Protein Differentially Affect Downregulation of MHC Class I and MICA/B Proteins

Sester

Koebernick

Owen

et al. 2009

The Journal of Immunology

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“…Outside the parasite, TcCRT may cross the parasitophorous vacuole and access the host cell cytoplasm. Once there, possibly through mechanisms similar to those used by virus or bacterial toxins, 41,42 it may access the host cell ER, where a competition with the host cell CRT is conceivable.…”

Section: Discussionmentioning

confidence: 99%

Trypanosoma cruzi Calreticulin Topographical Variations in Parasites Infecting Murine Macrophages

González

Valck

Sánchez

et al. 2015

The American Society of Tropical Medicine and Hygiene

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Abstract. Trypanosoma cruzi calreticulin (TcCRT), a 47-kDa chaperone, translocates from the endoplasmic reticulum to the area of flagellum emergence. There, it binds to complement components C1 and mannan-binding lectin (MBL), thus acting as a main virulence factor, and inhibits the classical and lectin pathways. The localization and functions of TcCRT, once the parasite is inside the host cell, are unknown. In parasites infecting murine macrophages, polyclonal anti-TcCRT antibodies detected TcCRT mainly in the parasite nucleus and kinetoplast. However, with a monoclonal antibody (E2G7), the resolution and specificity of the label markedly improved, and TcCRT was detected mainly in the parasite kinetoplast. Gold particles, bound to the respective antibodies, were used as probes in electron microscopy. This organelle may represent a stopover and accumulation site for TcCRT, previous its translocation to the area of flagellum emergence. Finally, early during T. cruzi infection and by unknown mechanisms, an important decrease in the number of MHC-I positive host cells was observed.

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“…At this stage the MHC-I might not be further matured due to the following reasons: 1) The MHC-I has acquired a peptide that induces final MHC-I maturation, 2) the particular MHC-I allomorph is inherently less prone to, or binds a peptide not inducing full maturation but inducing a structure not able to integrate into the peptide-loading complex (PLC), or 3), the MHC-I integration into the PLC is prohibited by viral interference (Roder, Geironson et al 2008). However, for most HLA-I allomorphs the majority of MHC-I molecules are integrated into the PLC through binding to tapasin, where the late-stage maturation of the pMHC-I complex takes place.…”

Section: Mhc-i Matures and Is Loaded With Peptide Inside The Cellmentioning

confidence: 99%

“…These peptides are derived from the interior of the cell, and presented on MHC-I outside the cell on its membrane surface. Each MHC-I receptor binds and presents one small endogenous or foreign peptide, which is derived from within the cell, (Roder, Geironson et al 2008) and the entire ligand-receptor complex is termed a peptide-MHC-I complex (pMHC-I). Essentially, through their T cell receptor (TcR) the CTLs may recognize a particular pMHC-I on the cell surface of the presenting cell.…”

Section: Introductionmentioning

confidence: 99%

MHC Class I Quality Control

Martha¹,

López-Delgado²,

Valadez-Moctezuma³

et al. 2012

Histocompatibility

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Viral Proteins Interfering with Antigen Presentation Target the Major Histocompatibility Complex Class I Peptide-Loading Complex

Cited by 24 publications

References 85 publications

Conserved Amino Acids within the Adenovirus 2 E3/19K Protein Differentially Affect Downregulation of MHC Class I and MICA/B Proteins

Conserved Amino Acids within the Adenovirus 2 E3/19K Protein Differentially Affect Downregulation of MHC Class I and MICA/B Proteins

Trypanosoma cruzi Calreticulin Topographical Variations in Parasites Infecting Murine Macrophages

MHC Class I Quality Control

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