ArticleImmunity2020
Butyrophilin-2A1 Directly Binds Germline-Encoded Regions of the Vγ9Vδ2 TCR and Is Essential for Phosphoantigen Sensing.
Article in Immunity, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 171 papers, 1 of them a synthesis that pooled it.
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Who cites it
171 citing papers in PubMed, 1 synthesis or guideline pooled it, 244 citations in OpenAlex.
- Glioblastoma cells potentiate the induction of the Th1-like profile in phosphoantigen-stimulated γδ T lymphocytes.Journal of neuro-oncology · 2021Pooled it
- Insights into the Mechanism of Action of Phosphoantigen Prodrugs on Vγ9Vδ2 T Cell Activation.ACS pharmacology & translational science · 2026Article
- γδ T cells and cancer.The Journal of clinical investigation · 2026Review
- Phosphoantigen-driven dissociation of butyrophilin oligomers activates γδ T cells.Cell discovery · 2026Article
- Review
- γδ T Cells at the Crossroads of Tuberculosis and COPD: From Early Immunity to Tissue Remodeling.International journal of molecular sciences · 2026Review
- A modular γδ TCR-T platform combining KRAS pMHC targeting with re-dosable mRNA engager redirection.Journal of hematology & oncology · 2026Article
- γδ T cells show distinct responses to CMV after stem cell transplantation.Journal of molecular medicine (Berlin, Germany) · 2026Article
- NanoBRET Saturation Analysis with a Novel HaloTag Ligand Reveals Butyrophilin Heteromeric Interactions Controlling γ9δ2 T Cell Activation.ACS chemical biology · 2026Article
- Selective Enrichment of Non-Canonical Vγ9-Jγ2 TRG Clonotypes in Clear Cell Renal Cell Carcinoma With Shorter CDR3 Loops.Immune network · 2026Article
- Harnessing the potential of γδ T cells through engineering and combination treatment for cancer therapies.Nature communications · 2026Review
- Innate-like T Cell Biology in the Tumor Microenvironment Implications for Cancer Immunotherapy.Cells · 2026Review
- Single-cell profiling reveals diverse γδ T cell subsets in ulcerative colitis.Science immunology · 2026Article
- Cell stress activates γ9δ2 T cells via endogenous phosphoantigens and butyrophilin complex dynamics.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- Inhibitory NK receptor expression associates with altered antimalarial function of γδ T cells.PLoS pathogens · 2026Article
- Vδ1 T-cell subset appears to be responsive to PD-1 blockade therapy and is associated with survival in melanoma.Journal for immunotherapy of cancer · 2026Article
- The Phylogenomic Approach Suggests That Butyrophilins Have Ligands Beyond Gamma-Delta Receptors.International journal of molecular sciences · 2026Article
- Multifaceted mechanisms of unconventional T cells in ischemia-reperfusion injury.Frontiers in immunology · 2026Review
- Revisiting the past in light of current knowledge on γδ T cells in leishmaniasis.Frontiers in immunology · 2026Review
- Beyond KIR and NKG2A blockade: reprogramming NK-cell immunity in solid tumors.Frontiers in cell and developmental biology · 2026Review
111 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 5 institutions in 3 countries.
Funding
Abstract
Vγ9Vδ2 T cells respond in a TCR-dependent fashion to both microbial and host-derived pyrophosphate compounds (phosphoantigens, or P-Ag). Butyrophilin-3A1 (BTN3A1), a protein structurally related to the B7 family of costimulatory molecules, is necessary but insufficient for this process. We performed radiation hybrid screens to uncover direct TCR ligands and cofactors that potentiate BTN3A1's P-Ag sensing function. These experiments identified butyrophilin-2A1 (BTN2A1) as essential to Vγ9Vδ2 T cell recognition. BTN2A1 synergised with BTN3A1 in sensitizing P-Ag-exposed cells for Vγ9Vδ2 TCR-mediated responses. Surface plasmon resonance experiments established Vγ9Vδ2 TCRs used germline-encoded Vγ9 regions to directly bind the BTN2A1 CFG-IgV domain surface. Notably, somatically recombined CDR3 loops implicated in P-Ag recognition were uninvolved. Immunoprecipitations demonstrated close cell-surface BTN2A1-BTN3A1 association independent of P-Ag stimulation. Thus, BTN2A1 is a BTN3A1-linked co-factor critical to Vγ9Vδ2 TCR recognition. Furthermore, these results suggest a composite-ligand model of P-Ag sensing wherein the Vγ9Vδ2 TCR directly interacts with both BTN2A1 and an additional ligand recognized in a CDR3-dependent manner.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.