# Microbe‐responsive human γδ T cells: the peculiar case of Staphylococcus aureus

## TL;DR

This paper reviews how human Vγ9/Vδ2 T cells respond to Staphylococcus aureus despite the bacteria not producing the usual activating metabolite.

## Contribution

The paper provides a comprehensive review of the unique immune response of Vγ9/Vδ2 T cells to S. aureus and explores unknown mechanisms.

## Key findings

- Vγ9/Vδ2 T cells respond to S. aureus even though it does not produce HMB-PP.
- The activation mechanism of these T cells by S. aureus remains largely unknown.
- Potential pathways and biological functions of this response are discussed.

## Abstract

Vγ9/Vδ2 T cells represent the largest γδ T‐cell population in human blood and possess a unique responsiveness towards microbial organisms by sensing the metabolite (E)‐4‐hydroxy‐3‐methyl‐but‐2‐enyl pyrophosphate (HMB‐PP) in the context of the butyrophilin family members BTN2A1 and BTN3A1. Curiously, the bacterium Staphylococcus aureus does not produce HMB‐PP but appears to be capable of inducing activation, cytokine expression and proliferation of Vγ9/Vδ2 T cells regardless, through a largely unknown mechanism. We here provide a comprehensive review of the existing literature around Vγ9/Vδ2 T‐cell responses to S. aureus and discuss potential pathways, ligands and biological functions.

Human Vγ9/Vδ2 T cells display a unique responsiveness towards microbial organisms producing the metabolite HMB‐PP. However, Staphylococcus aureus does not possess HMB‐PP but can induce activation, cytokine expression and proliferation of Vγ9/Vδ2 T cells regardless. We here discuss potential pathways, ligands and biological functions in this response to S. aureus.