Stress-associated antigens recognized by gamma delta T cell receptor (γδ TCR ligands)

Stress-associated antigens recognized by the gamma delta (γδ) T cell receptor (TCR) are a diverse set of molecules that act as indicators of cellular distress, including malignancy, infection, or oxidative stress (Nature Reviews Immunology, 2019). Unlike conventional αβ T cells that recognize peptide-MHC complexes, γδ T cells identify these antigens in a non-MHC-restricted manner, allowing for rapid immune responses (Frontiers in Immunology, 2020). Key ligands include MHC class I polypeptide-related sequence A and B (MICA/B), the UL16-binding protein (ULBP) family, and butyrophilin family members such as BTN3A1 and BTN2A1 (Journal for ImmunoTherapy of Cancer, 2021). These antigens are often overexpressed in various solid and hematological tumors, making them attractive targets for cancer immunotherapy. Therapeutic strategies include the use of bispecific antibodies that bridge γδ T cells to tumor-associated antigens or monoclonal antibodies that stabilize the active conformation of butyrophilins to trigger γδ T cell activation (LAVA Therapeutics, 2023). Understanding the regulation of these antigens is crucial for developing effective treatments that harness the innate-like cytotoxic potential of γδ T cells while minimizing risks like cytokine release syndrome.

Other names

Gamma delta T cell ligandsStress-induced ligandsMICA/BButyrophilinsPhosphoantigensUL16-binding proteins

Activation of gamma delta T cells through the engagement of the T cell receptor by stress-induced surface ligands or phosphoantigens.