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Viral Interference with Antigen Presentation Does Not Alter Acute or Chronic CD8 T Cell Immunodominance in Murine Cytomegalovirus Infection¹

Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239

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, m4+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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health (NIH) Grants AI47206 and AI50099 (to A.B.H.) and NIH Training Grant AI007472 (to M.W.M.).

² Address correspondence and reprint requests to Dr. Ann B. Hill, Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Mail Code L220, 3181 S.W. Sam Jackson Park Road, Portland OR 97239. E-mail address: hillan{at}ohsu.edu

³ Abbreviations used in this paper: MHC I, MHC class I; ER, endoplasmic reticulum; MCMV, murine CMV; wt, wild type; BM, bone marrow; DC, dendritic cell; ICS, intracellular cytokine staining; DRiP, defective ribosomal product.

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