Effective Control of Chronic γ-Herpesvirus Infection by Unconventional MHC Class Ia–Independent CD8 T Cells

PLoS Pathogens

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