Critical Role of an MHC Class I-Like/Innate-Like T Cell Immune Surveillance System in Host Defense against Ranavirus (Frog Virus 3) Infection.

Eva-Stina Isabella Edholm,Jacques Robert,Katherine Woo,Jinyeong Yim,Francisco De Jesús Andino

doi:10.3390/v11040330

Eva-Stina Isabella Edholm, Jacques Robert + Show 3 more

Open Access

PDF Available

https://doi.org/10.3390/v11040330

Copy DOI

Export

Save

Cite

Abstract
Highlights/Summary
Full-Text PDF
Similar Papers

Abstract

Listen

Besides the central role of classical Major Histocompatibility Complex (MHC) class Ia-restricted conventional Cluster of Differentiation 8 (CD8) T cells in antiviral host immune response, the amphibian Xenopus laevis critically rely on MHC class I-like (mhc1b10.1.L or XNC10)-restricted innate-like (i)T cells (iVα6 T cells) to control infection by the ranavirus Frog virus 3 (FV3). To complement and extend our previous reverse genetic studies showing that iVα6 T cells are required for tadpole survival, as well as for timely and effective adult viral clearance, we examined the conditions and kinetics of iVα6 T cell response against FV3. Using a FV3 knock-out (KO) growth-defective mutant, we found that upregulation of the XNC10 restricting class I-like gene and the rapid recruitment of iVα6 T cells depend on detectable viral replication and productive FV3 infection. In addition, by in vivo depletion with XNC10 tetramers, we demonstrated the direct antiviral effector function of iVα6 T cells. Notably, the transitory iVα6 T cell defect delayed innate interferon and cytokine gene response, resulting in long-lasting negative inability to control FV3 infection. These findings suggest that in Xenopus and likely other amphibians, an immune surveillance system based on the early activation of iT cells by non-polymorphic MHC class-I like molecules is important for efficient antiviral immune response.

Highlights

In mammals, potent adaptive immune response against viral pathogens largely depends on conventional Cluster of Differentiation (CD8) T cell effectors that express a broad T cell receptor (TCR)repertoire capable of recognizing a large array of antigens presented by polymorphic classical MajorHistocompatibility Complex (MHC) class I molecules
Because iVα6 T cells interact with the Major Histocompatibility Complex (MHC) class I-like molecule XNC10, we examined its gene expression profile
The present study provides new insights into the requirement for an effective amphibian host response to the ranavirus Frog virus 3 (FV3) trough, an early detection by the MHC class I-like XNC10, and the rapid recruitment of the activated XNC10-restricted innate T cell subset iVα6

Summary

Introduction

Potent adaptive immune response against viral pathogens largely depends on conventional Cluster of Differentiation (CD8) T cell effectors that express a broad T cell receptor (TCR)repertoire capable of recognizing a large array of antigens presented by polymorphic classical MajorHistocompatibility Complex (MHC) class I molecules (class Ia). Potent adaptive immune response against viral pathogens largely depends on conventional Cluster of Differentiation (CD8) T cell effectors that express a broad T cell receptor (TCR). It is increasingly appreciated that other unconventional or innate-like T cell effectors are critically involved in antiviral immunity [1]. These iT cells interact with non-polymorphic MHC class I-like molecules, have a limited or invariant T. Cells, which are restricted by the MHC class I-like molecule Cluster of Differentiation CD1d that presents lipids [2,3]. Deep-sequencing repertoire analysis has revealed the over-representation of 6 invariant

Methods

Results

Conclusion