scholarly journals Downregulation of Cell Surface Major Histocompatibility Complex Class I Expression Is Mediated by the Left-End Transcription Unit of Fowl Adenovirus 9

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2211
Author(s):  
Bryan D. Griffin ◽  
Juan Carlos Corredor ◽  
Yanlong Pei ◽  
Éva Nagy
Keyword(s):  
Major Histocompatibility Complex ◽  
Cell Surface ◽  
Major Histocompatibility Complex Class ◽  
Immune Evasion ◽  
Transcription Unit ◽  
Class I ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Mhc I ◽  
Histocompatibility Complex

Major histocompatibility complex class I (MHC-I) molecules play a critical role in the host’s antiviral response by presenting virus-derived antigenic peptides to cytotoxic T lymphocytes (CTLs), enabling the clearance of virus-infected cells. Human adenoviruses evade CTL-mediated cell lysis, in part, by interfering directly with the MHC-I antigen presentation pathway through the expression of E3-19K, which binds both MHC-I and the transporter associated with antigen processing protein and sequestering MHC-I within the endoplasmic reticulum. Fowl adenoviruses have no homologues of E3-19K. Here, we show that representative virus isolates of the species Fowl aviadenovirus C, Fowl aviadenovirus D, and Fowl aviadenovirus E downregulate the cell surface expression of MHC-I in chicken hepatoma cells, resulting in 71%, 11%, and 14% of the baseline expression level, respectively, at 12 h post-infection. Furthermore, this work reports that FAdV-9 downregulates cell surface MHC-I through a minimum of two separate mechanisms—a lysosomal-independent mechanism that requires the presence of the fowl adenovirus early 1 (FE1) transcription unit located within the left terminal genomic region between nts 1 and 6131 and a lysosomal-dependent mechanism that does not require the presence of FE1. These results establish a new functional role for the FE1 transcription unit in immune evasion. These studies provide important new information about the immune evasion of FAdVs and will enhance our understanding of the pathogenesis of inclusion body hepatitis and advance the progress made in next-generation FAdV-based vectors.

scholarly journals GRP78, a Coreceptor for Coxsackievirus A9, Interacts with Major Histocompatibility Complex Class I Molecules Which Mediate Virus Internalization

2002 ◽  
Vol 76 (2) ◽  
pp. 633-643 ◽  
Author(s):  
Kathy Triantafilou ◽  
Didier Fradelizi ◽  
Keith Wilson ◽  
Martha Triantafilou
Keyword(s):  
Major Histocompatibility Complex ◽  
Cell Surface ◽  
Major Histocompatibility Complex Class ◽  
Class I ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Class I Mhc ◽  
Mhc I ◽  
Histocompatibility Complex ◽  
Coxsackievirus A9

ABSTRACT It is becoming apparent that over the years cell infection by virus seems to have evolved into a multistep process in which many viruses employ distinct cell surface molecules for their attachment and cell entry. In this study the attachment and entry pathway of coxsackievirus A9 (CAV-9), a member of the Picornaviridae family, was investigated. It has been known that, although integrin αvβ3 is utilized as a receptor, its presence alone is insufficient for CAV-9 infection and that CAV-9 also requires a 70-kDa major histocompatibility complex class I (MHC-I)-associated protein (MAP-70) as a coreceptor molecule. We document by protein isolation and peptide sequencing that the 70-kDa protein is GRP78, a member of the heat shock protein 70 family of stress proteins. Furthermore we show by using fluorescence resonance energy transfer (FRET) that GRP78 is also expressed on the cell surface and associates with MHC-I molecules. In addition CAV-9 infection of permissive cells requires GRP78 and also MHC-I molecules, which are essential for virus internalization. The identification of GRP78 as a coreceptor for CAV-9 and the revelation of GRP78 and MHC-I associations have provided new insights into the life cycle of CAV-9, which utilizes integrin αvβ3 and GRP78 as receptor molecules whereas MHC-I molecules serve as the internalization pathway of this virus to mammalian cells.

Tim-3 Promotes Listeria monocytogenes Immune Evasion by Suppressing Major Histocompatibility Complex Class I

2019 ◽  
Author(s):  
Zhiding Wang ◽  
Ge Li ◽  
Shuaijie Dou ◽  
Yanling Zhang ◽  
Yiqiong Liu ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Listeria Monocytogenes ◽  
T Cell ◽  
Major Histocompatibility Complex Class ◽  
Immune Evasion ◽  
Class I ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Mhc I ◽  
Histocompatibility Complex

Abstract Background T-cell immunoglobulin and mucin protein 3 (Tim-3) is an immune checkpoint inhibitor that has therapeutic implications for many tumors and infectious diseases. However, the mechanisms by which Tim-3 promotes immune evasion remain unclear. Methods In this study, we demonstrated that Tim-3 inhibits the expression of major histocompatibility complex class I (MHC-I) in macrophages at both the messenger ribonucleic acid and protein levels by inhibiting the STAT1-NLRC5 signaling pathway. Results As a result, MHC-I-restricted antigen presentation by macrophages was inhibited by Tim-3 both in vitro and in a Listeria monocytogenes infection model in vivo. Systemic overexpression of Tim-3 or specific knockout of Tim-3 in macrophages significantly attenuated or enhanced CD8+ T-cell activation and infection damage in L monocytogenes-infected mice, respectively. Conclusions Thus, we identified a new mechanism by which Tim-3 promotes L monocytogenes immune evasion. Further studies on this pathway might shed new light on the physio-pathological roles of Tim-3 and suggest new approaches for intervention.

scholarly journals Metformin rescues cell surface major histocompatibility complex class I (MHC-I) deficiency caused by oncogenic transformation

Cell Cycle ◽  
2012 ◽  
Vol 11 (5) ◽  
pp. 865-870 ◽  
Author(s):  
Cristina Oliveras-Ferraros ◽  
Sílvia Cufí ◽  
Alejandro Vazquez-Martin ◽  
Octavio J. Menendez ◽  
Joaquim Bosch-Barrera ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Cell Surface ◽  
Major Histocompatibility Complex Class ◽  
Class I ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Oncogenic Transformation ◽  
Class I Mhc ◽  
Mhc I ◽  
Histocompatibility Complex

scholarly journals TAPBPR mediates peptide dissociation from MHC class I using a leucine lever

2018 ◽  
Author(s):  
F. Tudor Ilca ◽  
Andreas Neerincx ◽  
Clemens Hermann ◽  
Ana Marcu ◽  
Stefan Stevanovic ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Class I ◽  
Dependent Manner ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Mhc I ◽  
Histocompatibility Complex ◽  
Peptide Dissociation ◽  
Peptide Exchange

AbstractTapasin and TAPBPR are known to perform peptide editing on major histocompatibility complex class I (MHC I) molecules, however, the precise molecular mechanism(s) involved in this process remain largely enigmatic. Here, using immunopeptidomics in combination with novel cell-based assays that assess TAPBPR-mediate peptide exchange, we reveal a critical role for the K22-D35 loop of TAPBPR in mediating peptide exchange on MHC I. We identify a specific leucine within this loop that enables TAPBPR to facilitate peptide dissociation from MHC I. Moreover, we delineate the molecular features of the MHC I F pocket required for TAPBPR to promote peptide dissociation in a loop-dependent manner. These data reveal that chaperone-mediated peptide editing of MHC I can occur by different mechanisms dependent on the C-terminal residue that the MHC I accommodates in its F pocket and provide novel insights that may inform the therapeutic potential of TAPBPR manipulation to increase tumour immunogenicity.Impact StatementThis work demonstrates for the first time that the K22-D35 loop of TAPBPR is the essential region for mediating peptide exchange and peptide selection on major histocompatibility complex class I molecules.

Interferon beta modulates major histocompatibility complex class I (MHC I) and CD3-zeta expression in PC12 cells

2012 ◽  
Vol 513 (2) ◽  
pp. 223-228 ◽  
Author(s):  
Rodrigo Fabrizzio Inácio ◽  
Renata Graciele Zanon ◽  
Liana Verinaud ◽  
Alexandre Leite Rodrigues de Oliveira
Keyword(s):  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Pc12 Cells ◽  
Interferon Beta ◽  
Class I ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Class I Mhc ◽  
Mhc I ◽  
Histocompatibility Complex

scholarly journals A Mechanistic Basis for the Co-evolution of Chicken Tapasin and Major Histocompatibility Complex Class I (MHC I) Proteins

2013 ◽  
Vol 288 (45) ◽  
pp. 32797-32808 ◽  
Author(s):  
Andy van Hateren ◽  
Rachel Carter ◽  
Alistair Bailey ◽  
Nasia Kontouli ◽  
Anthony P. Williams ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Class I ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Class I Mhc ◽  
Mhc I ◽  
Histocompatibility Complex ◽  
Mechanistic Basis

scholarly journals Distinct Trafficking Pathways Mediate Nef-Induced and Clathrin-Dependent Major Histocompatibility Complex Class I Down-Regulation

2000 ◽  
Vol 74 (19) ◽  
pp. 9256-9266 ◽  
Author(s):  
Sylvie Le Gall ◽  
Florence Buseyne ◽  
Alicja Trocha ◽  
Bruce D. Walker ◽  
Jean-Michel Heard ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Class I ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Down Regulation ◽  
Class I Mhc ◽  
Mhc I ◽  
Heavy Chains ◽  
Histocompatibility Complex

ABSTRACT The human immunodeficiency virus type 1 Nef protein alters the post-Golgi stages of major histocompatibility complex class I (MHC-I) biogenesis. Presumed mechanisms involve the disclosure of a cryptic tyrosine-based sorting signal (YSQA) located in the cytoplasmic tail of HLA-A and -B heavy chains. We changed this signal for a prototypic sorting motif (YSQI or YSQL). Modified HLA-A2 molecules, termed A2-endo, displayed constitutively low surface levels and accumulated in a region close to or within the Golgi apparatus, a behavior reminiscent of wild-type HLA-A2 in Nef-expressing cells. However, several lines of evidence indicate that the action of prototypic signals on MHC-I trafficking differs from that of Nef. Internalization of surface A2-endo was more rapid and was associated with efficient recycling to the surface. A transdominant-negative mutant of dynamin-1 inhibited A2-endo constitutive internalization and Nef-induced CD4 down-regulation, whereas it did not affect the activity of Nef on MHC-I. Moreover, trafficking of A2-endo was still affected by the viral protein, indicating additive effects of prototypic signals and Nef. Therefore, distinct trafficking pathways regulate clathrin-dependent and Nef-induced MHC-I modulation.

Major histocompatibility complex class I-binding peptides are recycled to the cell surface after internalization

1993 ◽  
Vol 23 (12) ◽  
pp. 3224-3229 ◽  
Author(s):  
Ussama M. Abdel Motal ◽  
Xianzheng Zhou ◽  
Annalena Joki ◽  
Abdur Rehman Siddiqi ◽  
B. R. Srinivasa ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Cell Surface ◽  
Major Histocompatibility Complex Class ◽  
Class I ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Binding Peptides
Sign in / Sign up

Export Citation Format

Share Document