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Viral Interference with Antigen Presentation Does Not Alter Acute or Chronic CD8 T Cell Immunodominance in Murine Cytomegalovirus Infection

Michael W. Munks, Amelia K. Pinto, Carmen M. Doom and Ann B. Hill
J Immunol June 1, 2007, 178 (11) 7235-7241; DOI: https://doi.org/10.4049/jimmunol.178.11.7235
Michael W. Munks
Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239
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Amelia K. Pinto
Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239
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Carmen M. Doom
Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239
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Ann B. Hill
Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239
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Abstract

Both human CMV and murine CMV (MCMV) elicit large CD8 T cell responses, despite the potent effects of viral genes that interfere with the MHC class I (MHC I) pathway of Ag presentation. To investigate the impact of immune evasion on CD8 T cell priming, we infected mice with wild-type (wt) MCMV or a mutant lacking its MHC I immune evasion genes, Δm4+m6+m152 MCMV. In acute infection, the two viruses elicited a CD8 T cell response to 26 peptide epitopes that was virtually identical in total size, kinetics, and immunodominance hierarchy. This occurred despite results demonstrating that primary DCs are susceptible to the effects of MCMV’s MHC I immune evasion genes. Eight months later, responses to both wt and mutant MCMV displayed the same CD8 T cell “memory inflation” and altered immunodominance that characterize the transition to chronic MCMV infection in C57BL/6 mice. Taken together, these findings suggest either that cross-priming dominates over direct CD8 T cell priming in both acute and chronic MCMV infection, or else that the MHC I immune evasion genes of MCMV are unable to alter direct CD8 T cell priming in vivo. At 2 years postinfection, differences in CD8 T cell immunodominance emerged between individual mice, but on average there were only slight differences between wt and mutant virus infections. Overall, the data indicate that the presence or absence of MHC I immune evasion genes has remarkably little impact on the size or specificity of the MCMV-specific CD8 T cell response over an entire lifetime of infection.

  • Received May 9, 2006.
  • Accepted March 5, 2007.
  • Copyright © 2007 by The American Association of Immunologists
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The Journal of Immunology: 178 (11)
The Journal of Immunology
Vol. 178, Issue 11
1 Jun 2007
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Viral Interference with Antigen Presentation Does Not Alter Acute or Chronic CD8 T Cell Immunodominance in Murine Cytomegalovirus Infection
Michael W. Munks, Amelia K. Pinto, Carmen M. Doom, Ann B. Hill
The Journal of Immunology June 1, 2007, 178 (11) 7235-7241; DOI: 10.4049/jimmunol.178.11.7235

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Viral Interference with Antigen Presentation Does Not Alter Acute or Chronic CD8 T Cell Immunodominance in Murine Cytomegalovirus Infection
Michael W. Munks, Amelia K. Pinto, Carmen M. Doom, Ann B. Hill
The Journal of Immunology June 1, 2007, 178 (11) 7235-7241; DOI: 10.4049/jimmunol.178.11.7235
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