Inhibition of T cell receptor signal transduction by tyrosine kinase-interacting protein of Herpesvirus saimiri

The Journal of Experimental Medicine
Nam-hyuk ChoJae U Jung

Abstract

T cells play a central role in orchestrating immunity against pathogens, particularly viruses. Thus, impairing T cell activation is an important strategy employed by viruses to escape host immune control. The tyrosine kinase-interacting protein (Tip) of the T lymphotropic Herpesvirus saimiri (HVS) is constitutively present in lipid rafts and interacts with cellular Lck tyrosine kinase and p80 endosomal protein. Here we demonstrate that, due to the sequestration of Lck by HVS Tip, T cell receptor (TCR) stimulation fails to activate ZAP70 tyrosine kinase and to initiate downstream signaling events. TCR zeta chains in Tip-expressing T cells were initially phosphorylated to recruit ZAP70 molecule upon TCR stimulation, but the recruited ZAP70 kinase was not subsequently phosphorylated, resulting in TCR complexes that were stably associated with inactive ZAP70 kinase. Consequently, Tip expression not only markedly inhibited TCR-mediated intracellular signal transduction but also blocked TCR engagement with major histocompatibility complexes on the antigen-presenting cells and immunological synapse formation. These results demonstrate that a lymphotropic herpesvirus has evolved a novel mechanism to deregulate T cell activation to disa...Continue Reading

References

Sep 1, 1995·The Journal of Biological Chemistry·J U JungB Biesinger
Jan 28, 1998·Journal of Virology·S M DuboiseJ U Jung
May 27, 1999·Seminars in Cancer Biology·J U JungB Biesinger
Jun 22, 1999·Current Opinion in Immunology·J E van Leeuwen, L E Samelson
Jul 2, 1999·Springer Seminars in Immunopathology·M F Callan, A J McMichael
Apr 5, 2000·The Journal of Biological Chemistry·D A Hartley, G M Cooper
Feb 23, 2002·Science·Kyeong-Hee LeeAndrey S Shaw
Sep 24, 2002·Nature Immunology·Benjamin A FreibergAbraham Kupfer
Dec 4, 2003·Nature Reviews. Immunology·Johannes B Huppa, Mark M Davis
Dec 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gabriel Criado, Joaquín Madrenas

❮ Previous
Next ❯

Citations

Jun 19, 2008·Immunology and Cell Biology·Anja GlanzBrigitte Biesinger
Sep 27, 2008·Proceedings of the National Academy of Sciences of the United States of America·Pablo A GonzálezAlexis M Kalergis
Nov 16, 2010·Proceedings of the National Academy of Sciences of the United States of America·Nancy Van ProoyenGenoveffa Franchini
Feb 22, 2008·Journal of Virology·Keith R Jerome
Jan 27, 2012·Journal of Virology·Michaël LehouxJacques Archambault
Jul 30, 2005·Journal of Virology·Jens-Christian AlbrechtBrigitte Biesinger
Mar 6, 2012·Cell Communication and Signaling : CCS·Kristin KatschBrigitte Biesinger
Aug 21, 2008·Biological Chemistry·Claudia Haller, Oliver T Fackler
Nov 6, 2015·Journal of Immunology Research·Jean-Paul VernotDiego Fernando Martínez
May 21, 2016·Frontiers in Microbiology·Shuvomoy BanerjeeSubhash C Verma
Oct 19, 2016·Biochimica Et Biophysica Acta. Molecular Cell Research·Eun-Kyung KwonNam-Hyuk Cho
Aug 21, 2018·Cellular Microbiology·Rebecca J Bayliss, Vincent Piguet
Jan 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Derek D SloanKeith R Jerome
Apr 11, 2006·The Journal of General Virology·Melanie M Brinkmann, Thomas F Schulz

❮ Previous
Next ❯

Methods Mentioned

BETA
confocal microscopy
flow cytometry
flow
immunoprecipitation
ELISA

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.