The latest gamma-delta T cell paper

The latest Gamma-delta T cell paper that involves several former students and post-docs of ImmunoConcEpT lab. Congrats for this achievement!

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

Christelle HarlyStephen Paul JoyceCharlotte DomblidesThomas BacheletVincent PitardCharlotte MannatAngela PappalardoLionel CouziSonia NetzerLayal MassaraEmilie ObreOmar HawcharLydia LartigueStéphane ClaverolCarla CanoJean-François MoreauIsabelle MahoucheIsabelle SoubeyranRodrigue RossignolBenoit ViolletCarrie R WillcoxFiyaz MohammedBenjamin E WillcoxBenjamin FaustinJulie Déchanet-Merville.
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.

Sci Immunol. 2021 Jul 30;6(61):eaba9010. doi: 10.1126/sciimmunol.aba9010.

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