An MHC class Ib-restricted CD8 T cell response confers antiviral immunity

Phillip A. Swanson, Christopher D. Pack, Annette Hadley, Chyung Ru Wang, Iwona Stroynowski, Peter E. Jensen, Aron E. Lukacher

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1647-1657
Number of pages11
JournalJournal of Experimental Medicine
Volume205
Issue number7
DOIs
StatePublished - Jul 7 2008

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Major Histocompatibility Complex
Antiviral Agents
Immunity
Polyomavirus
T-Lymphocytes
Virus Diseases
Peptides
Viral Vaccines
Capsid Proteins
Haplotypes
Epitopes
Ligands
Antigens

ASJC Scopus subject areas

  • Immunology

Cite this

Swanson, P. A., Pack, C. D., Hadley, A., Wang, C. R., Stroynowski, I., Jensen, P. E., & Lukacher, A. E. (2008). An MHC class Ib-restricted CD8 T cell response confers antiviral immunity. Journal of Experimental Medicine, 205(7), 1647-1657. https://doi.org/10.1084/jem.20080570

An MHC class Ib-restricted CD8 T cell response confers antiviral immunity. / Swanson, Phillip A.; Pack, Christopher D.; Hadley, Annette; Wang, Chyung Ru; Stroynowski, Iwona; Jensen, Peter E.; Lukacher, Aron E.

In: Journal of Experimental Medicine, Vol. 205, No. 7, 07.07.2008, p. 1647-1657.

Research output: Contribution to journalArticle

Swanson, PA, Pack, CD, Hadley, A, Wang, CR, Stroynowski, I, Jensen, PE & Lukacher, AE 2008, 'An MHC class Ib-restricted CD8 T cell response confers antiviral immunity', Journal of Experimental Medicine, vol. 205, no. 7, pp. 1647-1657. https://doi.org/10.1084/jem.20080570
Swanson, Phillip A. ; Pack, Christopher D. ; Hadley, Annette ; Wang, Chyung Ru ; Stroynowski, Iwona ; Jensen, Peter E. ; Lukacher, Aron E. / An MHC class Ib-restricted CD8 T cell response confers antiviral immunity. In: Journal of Experimental Medicine. 2008 ; Vol. 205, No. 7. pp. 1647-1657.
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