γδ T cells recognize tumor cells via CDR3δ region

The principles governing γδ T cell specificity and diversity remain unclear due to lack of detailed structural analysis. To elucidate key structural basis of the specificity of γδ TCR for tumors, we analyzed the binding activities of synthesized TCR Vδ2 CDR3 peptides derived from tumor infiltrating lymphocyte (TIL) s in ovarian epithelial carcinoma (OEC) via biospecific interaction analysis approach, enzyme immunoassay and immunofluorescence assays. Besides, we used human CDR3δ grafted-Ig to repeat major tests. We found that synthesized OEC-derived CDR3δ peptides could bind specifically to tumor cell lines and tissues. CDR3δ-graft Ig showed a similar binding specificity with CDR3δ peptides, suggesting the determinant role of CDR3δ in antigen binding. Moreover, CDR3δ peptide-mediated binding specificity was blocked by pre-incubation with same peptide, which decreased the cytotoxicity of γδ T cells to OEC cells in vitro. Our finding indicates that CDR3δ peptide could mimic antigen-binding specificity of γδ TCR. Our strategy provides a novel, simple and convenient approach to investigate the binding activity and function of γδ TCR.