Suppression of antigen-specific T cell responses by the Kaposi's sarcoma-associated herpesvirus viral OX2 protein and its cellular orthologue, CD200

Misstear, K. and Chanas, S. A. and Rezaee, S. A. R. and Colman, R. and Quinn, L. L. and Long, H. M. and Goodyear, O. and Lord, J. M. and Hislop, A. D. and Blackbourn, D. J. (2012) Suppression of antigen-specific T cell responses by the Kaposi's sarcoma-associated herpesvirus viral OX2 protein and its cellular orthologue, CD200. Journal of Virology, 86 (11). pp. 6246-6257.

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Abstract

Regulating appropriate activation of the immune response in the healthy host despite continual immune surveillance dictates that immune responses must be either self-limiting and therefore negatively regulated following their activation or prevented from developing inappropriately. In the case of antigen-specific T cells, their response is attenuated by several mechanisms, including ligation of CTLA-4 and PD-1. Through the study of the viral OX2 (vOX2) immunoregulator encoded by Kaposi's sarcoma-associated herpesvirus (KSHV), we have identified a T cell-attenuating role both for this protein and for CD200, a cellular orthologue of the viral vOX2 protein. In vitro, antigen-presenting cells (APC) expressing either native vOX2 or CD200 suppressed two functions of cognate antigen-specific T cell clones: gamma interferon (IFN-γ) production and mobilization of CD107a, a cytolytic granule component and measure of target cell killing ability. Mechanistically, vOX2 and CD200 expression on APC suppressed the phosphorylation of ERK1/2 mitogen-activated protein kinase in responding T cells. These data provide the first evidence for a role of both KSHV vOX2 and cellular CD200 in the negative regulation of antigen-specific T cell responses. They suggest that KSHV has evolved to harness the host CD200-based mechanism of attenuation of T cell responses to facilitate virus persistence and dissemination within the infected individual. Moreover, our studies define a new paradigm in immune modulation by viruses: the provision of a negative costimulatory signal to T cells by a virus-encoded orthologue of CD200. © 2012, American Society for Microbiology.

Item Type: Article
Additional Information: Cited By :24 Export Date: 16 February 2020 CODEN: JOVIA Correspondence Address: Blackbourn, D.J.; School of Cancer Sciences, CR UK Centre for Cancer Research and MRC Centre for Immune Regulation, University of Birmingham, Birmingham, United Kingdom; email: d.j.blackbourn@bham.ac.uk
Uncontrolled Keywords: CD200 antigen CD200 receptor cytotoxic T lymphocyte antigen 4 gamma interferon lysosome associated membrane protein 1 mitogen activated protein kinase 1 mitogen activated protein kinase 3 protein OX2 unclassified drug virus protein antigens, CD200 G protein coupled receptor leukocyte antigen neuropeptide receptor orexin receptors virulence factor antigen expression antigen specificity article CD8+ T lymphocyte cell killing cellular distribution controlled study cytokine production down regulation enzyme inhibition enzyme phosphorylation expression vector human human cell Human herpesvirus 8 immunomodulation immunoregulation in vitro study lymphocyte proliferation lymphocyte subpopulation molecular cloning priority journal protein function protein localization protein protein interaction T lymphocyte activation virus attenuation virus immunity antigen presenting cell immunological tolerance immunology metabolism pathogenicity secretion T lymphocyte virology Harness Antigen-Presenting Cells Antigens, CD Herpesvirus 8, Human Humans Immune Tolerance Interferon-gamma Lysosomal-Associated Membrane Protein 1 Receptors, G-Protein-Coupled Receptors, Neuropeptide T-Lymphocytes Viral Proteins Virulence Factors
Subjects: QZ pathology-neoplasms-Genetics
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib5 lib5
Date Deposited: 14 May 2020 18:46
Last Modified: 14 May 2020 18:46
URI: http://eprints.mums.ac.ir/id/eprint/18973

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