Effective control of chronic γ-herpesvirus infection by unconventional MHC class Ia-independent CD8 T cells

Douglas C. Braaten, James Scott McClellan, Ilhem Messaoudi, Scott A. Tibbetts, Kelly B. McClellan, Janko Nikolich-Zugich, Herbert W. Virgin IV

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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-/-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-m-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. Copyright:

Original languageEnglish
Pages (from-to)394-407
Number of pages14
JournalPLoS pathogens
Issue number5
StatePublished - May 2006


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