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Journal of Virology, February 2000, p. 1871-1884, Vol. 74, No. 4
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
The Putative Natural Killer Decoy Early Gene
m04 (gp34) of Murine Cytomegalovirus Encodes an Antigenic
Peptide Recognized by Protective Antiviral CD8 T Cells
Rafaela
Holtappels,1
Doris
Thomas,1
Jürgen
Podlech,1
Gernot
Geginat,2
Hans-Peter
Steffens,1 and
Matthias J.
Reddehase1,*
Institute for Virology, Johannes Gutenberg
University, 55101 Mainz,1 and Institute
for Microbiology and Hygiene, Ruprecht Karls University Heidelberg,
68167 Mannheim,2 Germany
Received 15 September 1999/Accepted 24 November 1999
Several early genes of murine cytomegalovirus (MCMV) encode
proteins that mediate immune evasion by interference with the major
histocompatibility complex class I (MHC-I) pathway of antigen presentation to cytolytic T lymphocytes (CTL).
Specifically, the m152 gene product gp37/40 causes
retention of MHC-I molecules in the endoplasmic reticulum
(ER)-Golgi intermediate compartment. Lack of MHC-I on the cell surface
should activate natural killer (NK) cells recognizing the "missing
self." The retention, however, is counteracted by the m04
early gene product gp34, which binds to folded MHC-I molecules in the
ER and directs the complex to the cell surface. It was thus speculated
that gp34 might serve to silence NK cells and thereby complete the
immune evasion of MCMV. In light of these current views, we provide
here results demonstrating an in vivo role for gp34 in protective
antiviral immunity. We have identified an antigenic nonapeptide derived from gp34 and presented by the MHC-I molecule Dd.
Besides the immunodominant immediate-early nonapeptide consisting of
IE1 amino acids 168-176 (IE1168-176), the early nonapeptide m04243-251 is the second antigenic peptide described for
MCMV. The primary immune response to MCMV generates significant
m04-specific CD8 T-cell memory. Upon adoptive transfer into
immunodeficient recipients, an m04-specific CTL line controls MCMV
infection with an efficacy comparable to that of an IE1-specific CTL
line. Thus, gp34 is the first noted early protein
of MCMV that escapes viral immune evasion mechanisms. These data
document that MCMV is held in check by a redundance of protective CD8 T
cells recognizing antigenic peptides in different phases of viral gene expression.
*
Corresponding author. Mailing address: Institute for
Virology, Johannes Gutenberg University, Hochhaus am Augustusplatz,
55101 Mainz, Germany. Phone: 49-6131-39-33650. Fax: 49-6131-39-35604. E-mail: Matthias.Reddehase{at}uni-mainz.de.
Journal of Virology, February 2000, p. 1871-1884, Vol. 74, No. 4
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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