| First Author | Swanson PA 2nd | Year | 2008 |
| Journal | J Exp Med | Volume | 205 |
| Issue | 7 | Pages | 1647-57 |
| PubMed ID | 18541714 | Mgi Jnum | J:137349 |
| Mgi Id | MGI:3799379 | Doi | 10.1084/jem.20080570 |
| Citation | Swanson PA 2nd, et al. (2008) An MHC class Ib-restricted CD8 T cell response confers antiviral immunity. J Exp Med 205(7):1647-57 |
| abstractText | 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. |
