Sensing of cell stress by human γδ TCR-dependent recognition of annexin A2

Area of Science:

• Immunology
• Cell Biology
• Cancer Research

Background:

• Human γδ T cells are crucial for early defense against stressed cells via T-cell receptor (TCR) recognition.
• The specific molecular triggers and stress pathways underlying this recognition remain largely undefined.

Purpose of the Study:

• To identify the molecular ligands and stress pathways recognized by Vγ8Vδ3 TCR on stressed tumor cells.
• To investigate the role of annexin A2 as a potential ligand for γδ T cells in the context of oxidative stress.

Main Methods:

• Utilized a previously established strategy for identifying γδ TCR ligands.
• Exposed tumor cells to various stress conditions and analyzed Vγ8Vδ3 TCR recognition.
• Investigated annexin A2 expression and its interaction with γδ T cells, including proliferation assays and clone derivation.

Main Results:

• Vγ8Vδ3 TCR recognized tumor cells exposed to stress.
• Annexin A2 was identified as the direct ligand for Vγ8Vδ3 TCR.
• Annexin A2 expression on tumor cells was induced by stress in a reactive oxygen species-dependent manner.
• Purified annexin A2 stimulated proliferation of Vδ2^neg γδ T cells, and annexin A2-specific Vδ2^neg γδ T cell clones were generated.

Conclusions:

• Membrane exposure of annexin A2 serves as an oxidative stress signal for a subset of Vδ2^neg γδ T cells.
• This interaction suggests a role for annexin A2 in adaptive stress surveillance by γδ T cells in cancer contexts.