TY - JOUR
T1 - An MHC class Ib-restricted CD8 T cell response confers antiviral immunity
AU - Swanson, Phillip A.
AU - Pack, Christopher D.
AU - Hadley, Annette
AU - Wang, Chyung Ru
AU - Stroynowski, Iwona
AU - Jensen, Peter E.
AU - Lukacher, Aron E.
PY - 2008/7/7
Y1 - 2008/7/7
N2 - 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 (Kb-/-D b-/-) mice efficiently control this persistently infecting mouse pathogen. CD8 T cell depletion mitigates clearance of PyV in K b-/-Db-/- mice. We identified the ligand for PyV-specif c CD8 T cells in Kb-/-Db-/- 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-specif c CD8αβ T cells in Kb-/-Db-/- mice. Importantly, we demonstrate that Q9-VP2 - specif c CD8 T cells more effectively clear wild-type PyV than a VP2 epitopenull mutant PyV. Finally, we show that wild-type mice also generate Q9-restricted VP2 epitope - specif c 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.
AB - 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 (Kb-/-D b-/-) mice efficiently control this persistently infecting mouse pathogen. CD8 T cell depletion mitigates clearance of PyV in K b-/-Db-/- mice. We identified the ligand for PyV-specif c CD8 T cells in Kb-/-Db-/- 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-specif c CD8αβ T cells in Kb-/-Db-/- mice. Importantly, we demonstrate that Q9-VP2 - specif c CD8 T cells more effectively clear wild-type PyV than a VP2 epitopenull mutant PyV. Finally, we show that wild-type mice also generate Q9-restricted VP2 epitope - specif c 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.
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U2 - 10.1084/jem.20080570
DO - 10.1084/jem.20080570
M3 - Article
C2 - 18541714
AN - SCOPUS:46949090374
SN - 0022-1007
VL - 205
SP - 1647
EP - 1657
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 7
ER -