作者
Christelle Harly,Stephen Paul Joyce,Charlotte Domblides,Thomas Bachelet,Vincent Pitard,Charlotte Mannat,Angela Pappalardo,Lionel Couzi,Sonia Netzer,Layal Massara,Émilie Obre,Omar Hawchar,Lydia Lartigue,Stéphane Claverol,Carla E. Cano,Jean-François Moreau,Isabelle Mahouche,Isabelle Soubeyran,Rodrigue Rossignol,Benoı̂t Viollet,Carrie R. Willcox,Fiyaz Mohammed,Benjamin E. Willcox,Benjamin Faustin,Julie Déchanet‐Merville
摘要
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.