Altered Expression of TAP-1 and Major Histocompatibility Complex Class I in Laryngeal Papillomatosis: Correlation of TAP-1 with Disease

ABSTRACT Recurrent respiratory papillomatosis (RRP) is an insidious disease caused by human papillomavirus (HPV) infection. It is characterized by a variable clinical course that can include frequent disease recurrence, significant morbidity, and occasional mortality. The mechanisms responsible for the variability in the clinical course and the persistence of latent HPV infection remain unknown. Effective T-cell-mediated clearance of HPV-infected cells may be defective in patients with RRP, leading to recurrent disease and failure to suppress latent HPV reactivation. This study describes the down-regulation of the transporter associated with antigen presentation (TAP-1) and the major histocompatibility complex (MHC) class I protein expression in laryngeal papilloma tissue biopsies and cell culture of primary explants. There was a statistically significant correlation between reduction of TAP-1 expression in biopsy tissues and rapid recurrence of disease. Patients with RRP had less frequent recurrence if their papillomas expressed TAP-1 at levels close to that of normal tissue, compared with those with very low expression of TAP-1, who had frequent recurrence (32 versus 5 weeks to the next surgical intervention). These findings suggest that HPV may evade immune recognition by down-regulating class I MHC cell surface expression via decreased TAP-1 levels. Expression of TAP-1 could be used for prognostic evaluation of disease severity. Gamma interferon was able to restore class I MHC expression at the surfaces of laryngeal papilloma cells in culture. This up-regulation of class I MHC antigen at the cell surface potentially allows the infected cell to become a target for the immune system again. This finding provides some promise for nonsurgical treatment of laryngeal papillomas.

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

Journal of Virology ◽

10.1128/jvi.76.2.633-643.2002 ◽

2002 ◽

Vol 76 (2) ◽

pp. 633-643 ◽

Cited By ~ 125

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.

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Human Cytomegalovirus-Encoded Immune Modulators Partner To Downregulate Major Histocompatibility Complex Class I Molecules

Journal of Virology ◽

10.1128/jvi.01324-08 ◽

2008 ◽

Vol 83 (3) ◽

pp. 1359-1367 ◽

Cited By ~ 15

Author(s):

Vanessa M. Noriega ◽

Domenico Tortorella

Keyword(s):

Major Histocompatibility Complex ◽

Cell Surface ◽

Mhc Class I ◽

Human Cytomegalovirus ◽

Class I ◽

Immune Recognition ◽

Major Histocompatibility ◽

Histocompatibility Complex ◽

Presentation Pathway ◽

In Cells

ABSTRACT Throughout the course of natural evolution with its host, the human cytomegalovirus (HCMV) has developed a variety of strategies to avoid immune recognition and clearance. The major histocompatibility complex (MHC) class I antigen presentation pathway is a major target of the virus. HCMV encodes at least six gene products that modulate the processing of endoplasmic reticulum (ER)-resident MHC class I molecules. Here, we show that two virus-encoded proteins, US2 and US3, coordinate their functions toward the common goal of attenuating class I protein surface expression. In cells stably expressing both US2 and US3, class I molecules were almost completely downregulated from the cell surface. In addition, pulse-chase analysis revealed that the proteasome-dependent turnover of class I molecules occurs more rapidly in cells expressing both US2 and US3 than either US2 or US3 alone. The ability of US3 to retain class I molecules in the ER produces a target-rich environment for US2 to mediate the destruction of class I heavy chains. In fact, expression of US3 enhanced the association between US2 and class I molecules, thus encouraging their dislocation and degradation. This immune evasion strategy ensures that viral antigens are not presented on the cell surface during the early phase of HCMV infection, a critical time of replication and viral proliferation.

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Human Herpesvirus 7 U21 Downregulates Classical and Nonclassical Class I Major Histocompatibility Complex Molecules from the Cell Surface

Journal of Virology ◽

10.1128/jvi.01782-09 ◽

2010 ◽

Vol 84 (8) ◽

pp. 3738-3751 ◽

Cited By ~ 20

Author(s):

Nathan A. May ◽

Nicole L. Glosson ◽

Amy W. Hudson

Keyword(s):

Major Histocompatibility Complex ◽

Cell Surface ◽

Infected Cell ◽

Nk Cell ◽

Human Herpesvirus ◽

Class I ◽

Major Histocompatibility ◽

Class I Mhc ◽

Mhc Molecules ◽

Histocompatibility Complex

ABSTRACT Herpesviruses have evolved numerous strategies to evade detection by the immune system. Notably, most of the herpesviruses interfere with viral antigen presentation to cytotoxic T lymphocytes (CTLs) by removing class I major histocompatibility complex (MHC) molecules from the infected cell surface. Clearly, since the herpesviruses have evolved an extensive array of mechanisms to remove class I MHC molecules from the cell surface, this strategy serves them well. However, class I MHC molecules often serve as inhibitory ligands for NK cells, so viral downregulation of all class I MHC molecules should leave the infected cell open to NK cell attack. Some viruses solve this problem by selectively downregulating certain class I MHC products, leaving other class I products at the cell surface to serve as inhibitory NK cell ligands. Here, we show that human herpesvirus 7 (HHV-7) U21 binds to and downregulates all of the human class I MHC gene products, as well as the murine class I molecule H-2Kb. HHV-7-infected cells must therefore possess other means of escaping NK cell detection.

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

Cell Cycle ◽

10.4161/cc.11.5.19252 ◽

2012 ◽

Vol 11 (5) ◽

pp. 865-870 ◽

Cited By ~ 24

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

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Novel full-length major histocompatibility complex class I allele discovery and haplotype definition in pig-tailed macaques

10.1101/186494 ◽

2017 ◽

Author(s):

Matthew R. Semler ◽

Roger W. Wiseman ◽

Julie A. Karl ◽

Michael E. Graham ◽

Samantha M. Gieger ◽

...

Keyword(s):

Major Histocompatibility Complex ◽

Full Length ◽

Class I ◽

Major Histocompatibility ◽

Class I Mhc ◽

Mhc I ◽

Pacific Biosciences ◽

Histocompatibility Complex ◽

Immunodeficiency Virus ◽

The Impact

AbstractPig-tailed macaques (Macaca nemestrina, Mane) are important models for human immunodeficiency virus (HIV) studies. Their infectability with minimally modified HIV makes them a uniquely valuable animal model to mimic human infection with HIV and progression to acquired immunodeficiency syndrome (AIDS). However, variation in the pig-tailed macaque major histocompatibility complex (MHC) and the impact of individual transcripts on the pathogenesis of HIV and other infectious diseases is understudied compared to rhesus and cynomolgus macaques. In this study, we used Pacific Biosciences single-molecule real-time circular consensus sequencing to describe full-length MHC class I (MHC-I) transcripts for 194 pig-tailed macaques from three breeding centers. We then used the full-length sequences to inferMane-AandMane-Bhaplotypes containing groups of MHC-I transcripts that co-segregate due to physical linkage. In total, we characterized full-length open reading frames (ORFs) for 313Mane-A,Mane-B, andMane-Isequences that defined 86Mane-Aand 106Mane-BMHC-I haplotypes. Pacific Biosciences technology allows us to resolve theseMane-AandMane-Bhaplotypes to the level of synonymous allelic variants. The newly defined haplotypes and transcript sequences containing full-length ORFs provide an important resource for infectious disease researchers as certain MHC haplotypes have been shown to provide exceptional control of simian immunodeficiency virus (SIV) replication and prevention of AIDS-like disease in nonhuman primates. The increased allelic resolution provided by Pacific Biosciences sequencing also benefits transplant research by allowing researchers to more specifically match haplotypes between donors and recipients to the level of nonsynonymous allelic variation, thus reducing the risk of graft-versus-host disease.

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Characterization of a Murine Cytomegalovirus Class I Major Histocompatibility Complex (MHC) Homolog: Comparison to MHC Molecules and to the Human Cytomegalovirus MHC Homolog

Journal of Virology ◽

10.1128/jvi.72.1.460-466.1998 ◽

1998 ◽

Vol 72 (1) ◽

pp. 460-466 ◽

Cited By ~ 44

Author(s):

Tara L. Chapman ◽

Pamela J. Bjorkman

Keyword(s):

Major Histocompatibility Complex ◽

Heavy Chain ◽

Class I ◽

Major Histocompatibility ◽

Class I Mhc ◽

Endogenous Peptides ◽

Β2 Microglobulin ◽

Mhc Molecules ◽

Histocompatibility Complex ◽

Infected Cells

ABSTRACT Both human and murine cytomegaloviruses (HCMV and MCMV) down-regulate expression of conventional class I major histocompatibility complex (MHC) molecules at the surfaces of infected cells. This allows the infected cells to evade recognition by cytotoxic T cells but leaves them susceptible to natural killer cells, which lyse cells that lack class I molecules. Both HCMV and MCMV encode class I MHC heavy-chain homologs that may function in immune response evasion. We previously showed that a soluble form of the HCMV class I homolog (UL18) expressed in Chinese hamster ovary cells binds the class I MHC light-chain β2-microglobulin and a mixture of endogenous peptides (M. L. Fahnestock, J. L. Johnson, R. M. R. Feldman, J. M. Neveu, W. S. Lane, and P. J. Bjorkman, Immunity 3:583–590, 1995). Consistent with this observation, sequence comparisons suggest that UL18 contains the well-characterized groove that serves as the binding site in MHC molecules for peptides derived from endogenous and foreign proteins. By contrast, the MCMV homolog (m144) contains a substantial deletion within the counterpart of its α2 domain and might not be expected to contain a groove capable of binding peptides. We have now expressed a soluble version of m144 and verified that it forms a heavy chain–β2-microglobulin complex. By contrast to UL18 and classical class I MHC molecules, m144 does not associate with endogenous peptides yet is thermally stable. These results suggest that UL18 and m144 differ structurally and might therefore serve different functions for their respective viruses.

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