AI Article Synopsis
- Human γδ T cells play a role in maintaining tissue health and monitoring stress in epithelial cells, but their specific functions are not fully understood.
- Researchers discovered that the ephrin type-A receptor 2 (EphA2) is a stress antigen that human Vγ9Vδ1 T cells recognize, which activates the TCR in conjunction with ephrin A.
- The study found that increased expression of EphA2 in cancer cells, driven by metabolic changes, correlates with greater infiltration of CD3 T cells in colorectal cancer, suggesting γδ T cells can detect metabolic shifts related to viral infections or tumors.
Article 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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1126/sciimmunol.aba9010 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!