Gamma delta (γδ) T cells are essential to protective immunity. In humans, most γδ T cells express Vγ9Vδ2+ T cell receptors (TCRs) that respond to phosphoantigens (pAgs) produced by cellular pathogens and overexpressed by cancers. However, the molecular targets recognized by these γδTCRs are unknown. Here, we identify butyrophilin 2A1 (BTN2A1) as a key ligand that binds to the Vγ9+ TCR γ chain. BTN2A1 associates with another butyrophilin, BTN3A1, and these act together to initiate responses to pAg. Furthermore, binding of a second ligand, possibly BTN3A1, to a separate TCR domain incorporating Vδ2 is also required. This distinctive mode of Ag-dependent T cell activation advances our understanding of diseases involving pAg recognition and creates opportunities for the development of γδ T cell–based immunotherapies.
Image-guided
photothermal therapy (PTT) is an attractive strategy
to improve the diagnosis accuracy and treatment outcomes by monitoring
the accumulation of photothermal agents in tumors in real-time and
determining the best treatment window. Taking advantage of the superior
imaging quality of NIR-II fluorescence imaging and remote-controllable
phototherapy modality of PTT, we developed a facile macromolecular
fluorophore (PF) by conjugating a small-molecule NIR-II fluorophore
(Flav7) with an amphiphilic polypeptide. The PF can form uniform micelles
in aqueous solution, which exhibit a slight negative charge. In vitro experimental results showed that the PF nanoparticles
showed satisfactory photophysical properties, prominent photothermal
conversion efficiency (42.3%), excellent photothermal stability, negligible
cytotoxicity, and photothermal toxicity. Meanwhile, the PF can visualize
and feature the tumors by NIR-II fluorescence imaging owing to prolonged
blood circulation time and enhanced accumulation in tumors. Moreover, in vivo studies revealed that the PF nanoparticles achieved
an excellent photothermal ablation effect on tumors with a low dose
of NIR-II dye and light irradiation, and the process can be traced
by NIR fluorescence imaging.
An efficient pH-responsive multifunctional polypeptide micelle for simultaneous imaging and in vitro photodynamic therapy (PDT) has been prepared. The goal here is to detect and treat cancer cells by near-infrared fluorescence (NIRF) imaging and PDT synchronously. A photosensitizer BODIPY-Br2 with efficient singlet oxygen generation was synthesized at first which owns both seductive abilities in fluorescence emission and reactive oxygen species (ROS) generation under light irradiation. Then, amphiphilic copolymer micelles pH-triggered disassembly were synthesized from N-carboxyanhydride (NCA) monomer via a ring-opening polymerization and click reaction for the loading of BODIPY-Br2 by hydrophobic interaction, and the driving force is the protonation of the diisopropylethylamine groups conjugated to the polypeptide side chains. In vitro tests performed on HepG2 cancer cells confirm that the cell suppression rate was improved by more than 40% in the presence of light in the presence of an extremely low energy density (12 J/cm(2)) with very low concentration of 5.4 μM photosensitizer. At the same time, the internalization of the nanoparticles by cells can also be traced by NIRF imaging, indicating that the NIR nanoparticles presented imaging guided photodynamic therapy properties. It provides the potential of using polypeptide as a biodegradable carrier for NIR image-guided photodynamic therapy.
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