Tracking antigen-specific CD8+ T cells in the rat using MHC class I multimers

Area of Science:

• Immunology
• Virology
• Neuroscience

Background:

• Antigen-specific CD8(+) T cells are crucial for immune responses against microbes, tumors, and self-antigens.
• Major histocompatibility complex (MHC) multimer technology enables the study of these cells but was previously unavailable for rats.
• Borna disease virus (BDV) causes persistent central nervous system infections in rats, leading to immune-mediated neurological disease driven by CD8(+) T cells.

Purpose of the Study:

• To generate the first rat MHC multimer for detecting antigen-specific CD8(+) T cells.
• To characterize the antiviral CD8(+) T cell response to Borna disease virus (BDV) in rats using this new tool.

Main Methods:

• Production of a rat RT1(l) Pro5 MHC Pentamer loaded with an immunodominant peptide from the BDV nucleoprotein.
• Ex vivo flow cytometry analysis of CD8(+) T cells from the brains of BDV-infected Lewis rats (RT1(l) haplotype).
• Assessment of Pentamer-positive cell frequency and distribution in infected rats.

Main Results:

• The study successfully generated a novel rat MHC Pentamer specific for a BDV epitope.
• BDV-specific CD8(+) T cells (3-12% of CD8(+) T cells) were detected in the brains of infected rats.
• The frequency of these cells increased after in vitro culture, and they were primarily found in the brain, not peripheral organs.

Conclusions:

• The developed rat MHC Pentamer is a valuable tool for studying antigen-specific CD8(+) T cell responses in rats.
• This technology facilitates research into viral infections like BDV and their associated neuroinflammation.
• It enables the detection, isolation, and characterization of T cell responses in a relevant animal model.