Mohindar's Gamma Delta (γ9δ2) T cell lab
Mohindar's Gamma Delta (γ9δ2) T cell lab
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Human Vγ9Vδ2 T cells, their immune responses and challenges
Vγ9Vδ2 T cells act as sentinels of cellular stress, rapidly recognising infected or cancerous cells through changes in cellular metabolism and the accumulation of phosphoantigens (PAgs) such as IPP and HMBPP. Through a butyrophilin (BTN)-dependent sensing mechanism, they directly eliminate diseased cells while secreting cytokines that orchestrate communication with other immune populations. Through this dual role as killers and immune regulators, Vγ9Vδ2 T cells make important contributions to host defence and immunosurveillance. Intriguingly, these cells are absent in rodents, highlighting the distinct nature of human immunity and the need for innovative experimental approaches. Their exceptional therapeutic potential has generated considerable interest in exploiting them for the treatment of cancer and infectious diseases.
Despite their remarkable therapeutic potential, many fundamental questions remain unanswered.
What molecular cues enable Vγ9Vδ2 T cells to detect cellular stress while maintaining tolerance to healthy tissues?
How do certain tumours and pathogens successfully evade their responses?
And how have these mechanisms evolved across different species?
Our laboratory seeks to address these questions by integrating molecular immunology, comparative biology, and translational research. We aim to uncover the principles governing Vγ9Vδ2 T-cell activation, understand the evolutionary origins of these immune mechanisms, and explore how butyrophilin proteins shape immune responses in infection and cancer.
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