PLoS Pathogens | |
Effective Control of Chronic γ-Herpesvirus Infection by Unconventional MHC Class Ia–Independent CD8 T Cells | |
Kelly B McClellan1  Herbert W Virgin IV2  Scott A Tibbetts2  James Scott McClellan2  Ilhem Messaoudi3  Douglas C Braaten3  Janko Nikolich-Zugich3  | |
[1] Department of Microbiology and Immunology, Oregon Health and Science University, Beaverton, Oregon, United States of America;Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America;Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America | |
关键词: T cells; Cytotoxic T cells; Viral persistence; latency; Viral replication; Flow cytometry; Major histocompatibility complex; Viral transmission; infection; Spleen; | |
DOI : 10.1371/journal.ppat.0020037 | |
学科分类:生物科学(综合) | |
来源: Public Library of Science | |
【 摘 要 】
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.
【 授权许可】
CC BY
【 预 览 】
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