T细胞受体
生物
T细胞
主要组织相容性复合体
细胞生物学
内皮蛋白C受体
抗原
分子生物学
遗传学
免疫系统
免疫学
血小板
凝血酶
作者
Carrie R. Willcox,Pierre Vantourout,Mahboob Salim,Iva Zlatareva,Daisy Melandri,Leonor Zanardo,Roger George,Svend Kjær,Mark Jeeves,Fiyaz Mohammed,Adrian Hayday,Benjamin E. Willcox
出处
期刊:Immunity
[Elsevier]
日期:2019-11-01
卷期号:51 (5): 813-825.e4
被引量:102
标识
DOI:10.1016/j.immuni.2019.09.006
摘要
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.
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