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¹ Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322
² Department of Pathology, University of Chicago, Chicago, IL 60637
³ Center for Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390
⁴ Department of Pathology, University of Utah, Salt Lake City, UT 84112

CORRESPONDENCE Aron E. Lukacher: alukach{at}emory.edu

Although immunity against intracellular pathogens is primarily provided by CD8 T lymphocytes that recognize pathogen-derived peptides presented by major histocompatibility complex (MHC) class Ia molecules, MHC class Ib–restricted CD8 T cells have been implicated in antiviral immunity. Using mouse polyoma virus (PyV), we found that MHC class Ia–deficient (K^b–/–D^b–/–) mice efficiently control this persistently infecting mouse pathogen. CD8 T cell depletion mitigates clearance of PyV in K^b–/–D^b–/– mice. We identified the ligand for PyV-specific CD8 T cells in K^b–/–D^b–/– mice as a nonamer peptide from the VP2 capsid protein presented by Q9, a member of the β₂ microglobulin–associated Qa-2 family. Using Q9-VP2 tetramers, we monitored delayed but progressive expansion of these antigen-specific CD8β T cells in K^b–/–D^b–/– mice. Importantly, we demonstrate that Q9-VP2–specific CD8 T cells more effectively clear wild-type PyV than a VP2 epitope^null mutant PyV. Finally, we show that wild-type mice also generate Q9-restricted VP2 epitope–specific CD8 T cells to PyV infection. To our knowledge, this is the first evidence for a defined MHC class Ib–restricted antiviral CD8 T cell response that contributes to host defense. This study motivates efforts to uncover MHC class Ib–restricted CD8 T cell responses in other viral infections, and given the limited polymorphism of MHC class Ib molecules, it raises the possibility of developing peptide-based viral vaccines having broad coverage across MHC haplotypes.

C.-R. Wang's present address is Dept. of Microbiology and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611.

© 2008 Swanson et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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