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

Misstear, K, Chanas, SA, Rezaee, SA, Colman, R, Quinn, LL, Long, HM, Goodyear, O, Lord, JM, Hislop, AD and Blackbourn, DJ (2012) Suppression of antigen-specific T cell responses by the Kaposi's sarcoma-associated herpesvirus viral OX2 protein and its cellular orthologue, CD200. J Virol, 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.

Item Type: Article
Authors :
NameEmailORCID
Misstear, KUNSPECIFIEDUNSPECIFIED
Chanas, SAUNSPECIFIEDUNSPECIFIED
Rezaee, SAUNSPECIFIEDUNSPECIFIED
Colman, RUNSPECIFIEDUNSPECIFIED
Quinn, LLUNSPECIFIEDUNSPECIFIED
Long, HMUNSPECIFIEDUNSPECIFIED
Goodyear, OUNSPECIFIEDUNSPECIFIED
Lord, JMUNSPECIFIEDUNSPECIFIED
Hislop, ADUNSPECIFIEDUNSPECIFIED
Blackbourn, DJd.blackbourn@surrey.ac.ukUNSPECIFIED
Date : June 2012
Identification Number : 10.1128/JVI.07168-11
Uncontrolled Keywords : 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
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 09:51
Last Modified : 17 May 2017 14:45
URI: http://epubs.surrey.ac.uk/id/eprint/825379

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