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- Title
Effective Control of Chronic γ-Herpesvirus Infection by Unconventional MHC Class Ia-Independent CD8 T Cells.
- Authors
Braaten, Douglas C.; McClellan, James Scott; Messaoudi, Ilhem; Tibbetts, Scott A.; McClellan, Kelly B.; Nikolich-Zugich, Janko; Virgin IV, Herbert W.
- Abstract
Control of virus infection is mediated in part by major histocompatibility complex (MHC) Class Ia presentation of viral peptides to conventional CD8 T cells. Although important, the absolute requirement for MHC Class Ia-dependent CD8 T cells for control of chronic virus infection has not been formally demonstrated. We show here that mice lacking MHC Class Ia molecules (Kb−/−xDb−/− mice) effectively control chronic γ-herpesvirus 68 (γHV68) infection via a robust expansion of β2-microglobulin (β2-m)-dependent, but CD1d-independent, unconventional CD8 T cells. These unconventional CD8 T cells expressed: (1) CD8αβ and CD3, (2) cell surface molecules associated with conventional effector/memory CD8 T cells, (3) TCRαβ with a significant Vβ4, Vβ3, and Vβ10 bias, and (4) the key effector cytokine interferon-γ (IFNγ). Unconventional CD8 T cells utilized a diverse TCR repertoire, and CDR3 analysis suggests that some of that repertoire may be utilized even in the presence of conventional CD8 T cells. This is the first demonstration to our knowledge that β2-m-dependent, but Class Ia-independent, unconventional CD8 T cells can efficiently control chronic virus infection, implicating a role for β2-n-dependent non-classical MHC molecules in control of chronic viral infection. We speculate that similar unconventional CD8 T cells may be able to control of other chronic viral infections, especially when viruses evade immunity by inhibiting generation of Class Ia-restricted T cells.
- Subjects
HERPESVIRUS diseases; VIRUS diseases; MAJOR histocompatibility complex; T cells; CYTOKINES
- Publication
PLoS Pathogens, 2006, Vol 2, Issue 5, pe37
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.0020037