The role of NKG2D signaling in inhibition of cytotoxic T-lymphocyte lysis by the murine cytomegalovirus immunoevasin m152/gp40

Amelia K. Pinto, Amanda M. Jamieson, David H. Raulet, Ann Hill

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Three proteins encoded by murine cytomegalovirus (MCMV)- gp34, encoded by m04 (m04/gp34), gp48, encoded by m06 (/n06/gp48), and gp40, encoded by m152 (m152/gp40) - act together to powerfully impact the ability of primed cytotoxic CD8 T lymphocytes (CTL) to kill virus-infected cells. Of these three, the impact of m152/gp40 on CTL lysis appears greater than would be expected based on its impact on cell surface major histocompatibility complex (MHC) class I. In addition to MHC class I, m152/gp40 also downregulates the RAE-1 family of NKG2D ligands, which can provide costimulation for CD8 T cells. We hypothesized that m152/gp40 may impact CTL lysis so profoundly because it inhibits both antigen presentation and NKG2D-mediated costimulation. We therefore tested the extent to which m152/gp40's ability to inhibit CTL lysis of MCMV-infected cells could be accounted for by its inhibition of NKG2D signaling. As was predictable from the results reported in the literature, NKG2D ligands were not detected by NKG2D tetramer staining of cells infected with wild-type MCMV, whereas those infected with MCMV lacking m152/gp40 displayed measurable levels of the NKG2D ligand. To determine whether NKG2D signaling contributed to the ability of CTL to lyse these cells, we used a blocking anti-NKG2D antibody. Blocking NKG2D signaling did affect the killing of MCMV-infected cells for some epitopes. However, for all epitopes, the impact of m152/gp40 on CTL lysis was much greater than the impact of inhibition of NKG2D signaling. We conclude that the downregulation of NKG2D ligands by MCMV makes only a small contribution to the impact of m152/gp40 on CTL lysis and only for a small subset of CTL.

Original languageEnglish (US)
Pages (from-to)12564-12571
Number of pages8
JournalJournal of Virology
Volume81
Issue number22
DOIs
StatePublished - Nov 2007

Fingerprint

Muromegalovirus
Cytomegalovirus
cytotoxic T-lymphocytes
Cytotoxic T-Lymphocytes
T-lymphocytes
T-Lymphocytes
mice
Ligands
Major Histocompatibility Complex
Epitopes
major histocompatibility complex
cells
Down-Regulation
epitopes
Blocking Antibodies
Antigen Presentation
T-Lymphocyte Subsets
antigen presentation
Anti-Idiotypic Antibodies
Staining and Labeling

ASJC Scopus subject areas

  • Immunology

Cite this

The role of NKG2D signaling in inhibition of cytotoxic T-lymphocyte lysis by the murine cytomegalovirus immunoevasin m152/gp40. / Pinto, Amelia K.; Jamieson, Amanda M.; Raulet, David H.; Hill, Ann.

In: Journal of Virology, Vol. 81, No. 22, 11.2007, p. 12564-12571.

Research output: Contribution to journalArticle

Pinto, Amelia K. ; Jamieson, Amanda M. ; Raulet, David H. ; Hill, Ann. / The role of NKG2D signaling in inhibition of cytotoxic T-lymphocyte lysis by the murine cytomegalovirus immunoevasin m152/gp40. In: Journal of Virology. 2007 ; Vol. 81, No. 22. pp. 12564-12571.
@article{b16b24bbc2154ab7b54f4c1518af3140,
title = "The role of NKG2D signaling in inhibition of cytotoxic T-lymphocyte lysis by the murine cytomegalovirus immunoevasin m152/gp40",
abstract = "Three proteins encoded by murine cytomegalovirus (MCMV)- gp34, encoded by m04 (m04/gp34), gp48, encoded by m06 (/n06/gp48), and gp40, encoded by m152 (m152/gp40) - act together to powerfully impact the ability of primed cytotoxic CD8 T lymphocytes (CTL) to kill virus-infected cells. Of these three, the impact of m152/gp40 on CTL lysis appears greater than would be expected based on its impact on cell surface major histocompatibility complex (MHC) class I. In addition to MHC class I, m152/gp40 also downregulates the RAE-1 family of NKG2D ligands, which can provide costimulation for CD8 T cells. We hypothesized that m152/gp40 may impact CTL lysis so profoundly because it inhibits both antigen presentation and NKG2D-mediated costimulation. We therefore tested the extent to which m152/gp40's ability to inhibit CTL lysis of MCMV-infected cells could be accounted for by its inhibition of NKG2D signaling. As was predictable from the results reported in the literature, NKG2D ligands were not detected by NKG2D tetramer staining of cells infected with wild-type MCMV, whereas those infected with MCMV lacking m152/gp40 displayed measurable levels of the NKG2D ligand. To determine whether NKG2D signaling contributed to the ability of CTL to lyse these cells, we used a blocking anti-NKG2D antibody. Blocking NKG2D signaling did affect the killing of MCMV-infected cells for some epitopes. However, for all epitopes, the impact of m152/gp40 on CTL lysis was much greater than the impact of inhibition of NKG2D signaling. We conclude that the downregulation of NKG2D ligands by MCMV makes only a small contribution to the impact of m152/gp40 on CTL lysis and only for a small subset of CTL.",
author = "Pinto, {Amelia K.} and Jamieson, {Amanda M.} and Raulet, {David H.} and Ann Hill",
year = "2007",
month = "11",
doi = "10.1128/JVI.01328-07",
language = "English (US)",
volume = "81",
pages = "12564--12571",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "22",

}

TY - JOUR

T1 - The role of NKG2D signaling in inhibition of cytotoxic T-lymphocyte lysis by the murine cytomegalovirus immunoevasin m152/gp40

AU - Pinto, Amelia K.

AU - Jamieson, Amanda M.

AU - Raulet, David H.

AU - Hill, Ann

PY - 2007/11

Y1 - 2007/11

N2 - Three proteins encoded by murine cytomegalovirus (MCMV)- gp34, encoded by m04 (m04/gp34), gp48, encoded by m06 (/n06/gp48), and gp40, encoded by m152 (m152/gp40) - act together to powerfully impact the ability of primed cytotoxic CD8 T lymphocytes (CTL) to kill virus-infected cells. Of these three, the impact of m152/gp40 on CTL lysis appears greater than would be expected based on its impact on cell surface major histocompatibility complex (MHC) class I. In addition to MHC class I, m152/gp40 also downregulates the RAE-1 family of NKG2D ligands, which can provide costimulation for CD8 T cells. We hypothesized that m152/gp40 may impact CTL lysis so profoundly because it inhibits both antigen presentation and NKG2D-mediated costimulation. We therefore tested the extent to which m152/gp40's ability to inhibit CTL lysis of MCMV-infected cells could be accounted for by its inhibition of NKG2D signaling. As was predictable from the results reported in the literature, NKG2D ligands were not detected by NKG2D tetramer staining of cells infected with wild-type MCMV, whereas those infected with MCMV lacking m152/gp40 displayed measurable levels of the NKG2D ligand. To determine whether NKG2D signaling contributed to the ability of CTL to lyse these cells, we used a blocking anti-NKG2D antibody. Blocking NKG2D signaling did affect the killing of MCMV-infected cells for some epitopes. However, for all epitopes, the impact of m152/gp40 on CTL lysis was much greater than the impact of inhibition of NKG2D signaling. We conclude that the downregulation of NKG2D ligands by MCMV makes only a small contribution to the impact of m152/gp40 on CTL lysis and only for a small subset of CTL.

AB - Three proteins encoded by murine cytomegalovirus (MCMV)- gp34, encoded by m04 (m04/gp34), gp48, encoded by m06 (/n06/gp48), and gp40, encoded by m152 (m152/gp40) - act together to powerfully impact the ability of primed cytotoxic CD8 T lymphocytes (CTL) to kill virus-infected cells. Of these three, the impact of m152/gp40 on CTL lysis appears greater than would be expected based on its impact on cell surface major histocompatibility complex (MHC) class I. In addition to MHC class I, m152/gp40 also downregulates the RAE-1 family of NKG2D ligands, which can provide costimulation for CD8 T cells. We hypothesized that m152/gp40 may impact CTL lysis so profoundly because it inhibits both antigen presentation and NKG2D-mediated costimulation. We therefore tested the extent to which m152/gp40's ability to inhibit CTL lysis of MCMV-infected cells could be accounted for by its inhibition of NKG2D signaling. As was predictable from the results reported in the literature, NKG2D ligands were not detected by NKG2D tetramer staining of cells infected with wild-type MCMV, whereas those infected with MCMV lacking m152/gp40 displayed measurable levels of the NKG2D ligand. To determine whether NKG2D signaling contributed to the ability of CTL to lyse these cells, we used a blocking anti-NKG2D antibody. Blocking NKG2D signaling did affect the killing of MCMV-infected cells for some epitopes. However, for all epitopes, the impact of m152/gp40 on CTL lysis was much greater than the impact of inhibition of NKG2D signaling. We conclude that the downregulation of NKG2D ligands by MCMV makes only a small contribution to the impact of m152/gp40 on CTL lysis and only for a small subset of CTL.

UR - http://www.scopus.com/inward/record.url?scp=36048951527&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36048951527&partnerID=8YFLogxK

U2 - 10.1128/JVI.01328-07

DO - 10.1128/JVI.01328-07

M3 - Article

C2 - 17855532

AN - SCOPUS:36048951527

VL - 81

SP - 12564

EP - 12571

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 22

ER -