CD16a pairs form the basal molecular subunit for the NK-cell ADCC lytic synapse

Area of Science:

• Immunology
• Cell Biology
• Nanotechnology

Background:

• Natural killer (NK) cells are crucial for immune defense against viral infections and cancer.
• Antibody-dependent cellular cytotoxicity (ADCC) is a key NK cell effector function.
• The precise molecular mechanisms, particularly the role of FcγRIIIa (CD16a) clustering, in ADCC remain incompletely understood.

Purpose of the Study:

• To investigate the spatial distribution and organization of CD16a on NK cells during ADCC.
• To elucidate the molecular basis of CD16a clustering and its role in NK cell activation.

Main Methods:

• Utilized MINFLUX nanoscopy for high-resolution imaging of CD16a distribution.
• Analyzed CD16a organization in resting and activated NK cells on supported lipid bilayers.
• Studied NK cell activation using Trastuzumab as a model antibody.

Main Results:

• Identified CD16a homodimers with an approximate 18 nm separation in both resting and activated NK cells.
• Observed a modest increase in CD16a clusters (≥4 localizations) upon NK cell activation.
• Found no significant change in CD16a pair distances, suggesting subtle structural rearrangements.

Conclusions:

• High-resolution imaging reveals CD16a homodimers and subtle clustering changes during NK cell activation.
• These structural modifications in CD16a organization likely play a role in mediating ADCC.
• Provides unprecedented spatial resolution for CD16a, advancing understanding of ADCC mechanisms.