An effective primary and memory CD8+ T cell response is directed towards an H-2Kb restricted HSV1-gB-SSIEFARL epitope in the experimentally infected zebrafish

Abstract

We sought to identify and characterize HSV1 specific CD8+ T cells in the experimentally infected zebrafish (zf), a model organism that offers real time tracking of cellular dynamics. We generated a fluorescently labelled class I MHC tetramer of zebrafish using an H-2Kb restricted peptide of gB protein of HSV1 (Uda-HSV1-gB-SSIEFARL-tetramer) for analysing the differentiation of virus-specific CD8+ T cell response. We show that the Uda-SSIEFARL-tetramer+CD8+ T cells rapidly expand in the lymphoid organs and are efficiently recruited to non-lymphoid tissues of HSV1 infected zebrafishes. The expanded cells upregulate effector cytokines; IFN-{gamma}, IL-2, TNF- and cytolyze SSIEFARL-peptide pulsed targets. Uda-SSIEFARL-tetramer+CD8+ T cells efficiently migrate to the infected tissues as demonstrated by fluorescent microscopy and in vivo imaging. The Uda-SSIEFARL-tetramer+ memory cells are recalled in the response following a secondary infection of zebrafish with HSV1. We, therefore, make a rather intriguing observation that zebrafishes infected with HSV1 generate an efficient CTL response against H-2Kb restricted HSV1-gB-SSIEFARL epitope despite their evolutionary divergence from mice [~]445 million years ago. We also argue that zebrafish could serve as a better accessible model organism for studying in vivo dynamics of virus-specific CD8+ T cells.