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Effective control of chronic gamma-herpesvirus infection by unconventional MHC Class Ia-independent CD8 T cells.

Author(s): Braaten Douglas C | McClellan James Scott | Messaoudi Ilhem | Tibbetts Scott A | McClellan Kelly B | Nikolich-Zugich Janko | Virgin Herbert W

Journal: PLoS Pathogens
ISSN 1553-7366

Volume: 2;
Issue: 5;
Start page: e37;
Date: 2006;
Original page

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 (K(b-/-)xD(b-/-) mice) effectively control chronic gamma-herpesvirus 68 (gammaHV68) infection via a robust expansion of beta2-microglobulin (beta2-m)-dependent, but CD1d-independent, unconventional CD8 T cells. These unconventional CD8 T cells expressed: (1) CD8alphabeta and CD3, (2) cell surface molecules associated with conventional effector/memory CD8 T cells, (3) TCRalphabeta with a significant Vbeta4, Vbeta3, and Vbeta10 bias, and (4) the key effector cytokine interferon-gamma (IFNgamma). 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 beta2-m-dependent, but Class Ia-independent, unconventional CD8 T cells can efficiently control chronic virus infection, implicating a role for beta2-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.
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