Your browser version may not work well with NCBI's Web applications. More information here...
1: J Exp Med. 2008 Jul 7;205(7):1647-57. Epub 2008 Jun 9.
Related Articles, Links
Click here to read Click here to read
An MHC class Ib-restricted CD8 T cell response confers antiviral immunity.

Swanson PA 2nd, Pack CD, Hadley A, Wang CR, Stroynowski I, Jensen PE, Lukacher AE.

Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA.

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 beta(2) microglobulin-associated Qa-2 family. Using Q9-VP2 tetramers, we monitored delayed but progressive expansion of these antigen-specific CD8alphabeta 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.

Publication Types:
PMID: 18541714 [PubMed - indexed for MEDLINE]

PMCID: PMC2442642 [Available on 01/07/09]