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Human γδ T cell sensing of AMPK-dependent metabolic tumor reprogramming through TCR recognition of EphA2

Abstract : Human γδ T cells contribute to tissue homeostasis and participate in epithelial stress surveillance through mechanisms that are not well understood. Here, we identified ephrin type-A receptor 2 (EphA2) as a stress antigen recognized by a human Vγ9Vδ1 TCR. EphA2 is recognized coordinately by ephrin A to enable γδ TCR activation. We identified a putative TCR binding site on the ligand-binding domain of EphA2 that was distinct from the ephrin A binding site. Expression of EphA2 was up-regulated upon AMP-activated protein kinase (AMPK)-dependent metabolic reprogramming of cancer cells, and coexpression of EphA2 and active AMPK in tumors was associated with higher CD3 T cell infiltration in human colorectal cancer tissue. These results highlight the potential of the human γδ TCR to cooperate with a co-receptor to recognize non-MHC-encoded proteins as signals of cellular dysregulation, potentially allowing γδ T cells to sense metabolic energy changes associated with either viral infection or cancer.
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https://www.hal.inserm.fr/inserm-03349495
Contributor : Elizabeth Bernardo Connect in order to contact the contributor
Submitted on : Monday, September 20, 2021 - 3:24:55 PM
Last modification on : Tuesday, May 17, 2022 - 1:58:08 PM
Long-term archiving on: : Tuesday, December 21, 2021 - 7:01:09 PM

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Christelle Harly, Stephen Paul, Charlotte Domblides, Thomas Bachelet, Vincent Pitard, et al.. Human γδ T cell sensing of AMPK-dependent metabolic tumor reprogramming through TCR recognition of EphA2. Science Immunology, American Association for the Advancement of Science (AAAS), 2021, 6 (61), pp.eaba9010. ⟨10.1126/sciimmunol.aba9010⟩. ⟨inserm-03349495⟩

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