An MHC class Ib-restricted CD8 T cell response confers antiviral immunity.
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.
Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Phillip A
PA
Swanson
Christopher D
CD
Pack
Annette
A
Hadley
Chyung-Ru
CR
Wang
Iwona
I
Stroynowski
Peter E
PE
Jensen
Aron E
AE
Lukacher
D000818:Animals; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D053918:Papillomavirus Vaccines / Q000235:genetics / Q000276:immunology; D011110:Polymorphism, Genetic / Q000276:immunology; D011120:Polyomavirus / Q000235:genetics / Q000276:immunology*; D027601:Polyomavirus Infections / Q000235:genetics / Q000276:immunology*
D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; C477867:CD8beta antigen; D036022:Capsid Proteins; D015395:Histocompatibility Antigens Class I; D053918:Papillomavirus Vaccines; C032907:Q surface antigens; C442543:VP2 protein, Polyomavirus