| Autor: |
Willcox, Carrie R, Vantourout, Pierre, Mahboob Salim, Zlatareva, Iva, Melandri, Daisy, Zanardo, Leonor, George, Roger, Kjaer, Svend, Jeeves, Mark, Fiyaz Mohammed, Hayday, Adrian C, Willcox, Benjamin E |
| Rok vydání: |
2020 |
| Předmět: |
|
| DOI: |
10.25418/crick.11637927 |
| Popis: |
Butyrophilin (BTN) and butyrophilin-like (BTNL/Btnl) heteromers are major regulators of human and mouse γδ T cell subsets, but considerable contention surrounds whether they represent direct γδ T cell receptor (TCR) ligands. We demonstrate that the BTNL3 IgV domain binds directly and specifically to a human Vγ4+ TCR, "LES" with an affinity (∼15-25 μM) comparable to many αβ TCR-peptide major histocompatibility complex interactions. Mutations in germline-encoded Vγ4 CDR2 and HV4 loops, but not in somatically recombined CDR3 loops, drastically diminished binding and T cell responsiveness to BTNL3-BTNL8-expressing cells. Conversely, CDR3γ and CDR3δ loops mediated LES TCR binding to endothelial protein C receptor, a clonally restricted autoantigen, with minimal CDR1, CDR2, or HV4 contributions. Thus, the γδ TCR can employ two discrete binding modalities: a non-clonotypic, superantigen-like interaction mediating subset-specific regulation by BTNL/BTN molecules and CDR3-dependent, antibody-like interactions mediating adaptive γδ T cell biology. How these findings might broadly apply to γδ T cell regulation is also examined. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
