Spatial localization of CD16a at the human NK cell ADCC lytic synapse.

Area of Science:

• Immunology
• Cell Biology
• Biophysics

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.
• FcγRIIIa (CD16a) engagement with IgG immune complexes mediates NK cell ADCC.

Purpose of the Study:

• To investigate the molecular basis of CD16a clustering and its role in NK cell ADCC.
• To visualize the spatial organization of CD16a on the NK cell membrane at high resolution.

Main Methods:

• MINFLUX nanoscopy was employed to map the distribution of stoichiometrically labeled CD16a.
• NK cells were activated on supported lipid bilayers using Trastuzumab to mimic immune synapse formation.

Main Results:

• MINFLUX nanoscopy revealed pairs of CD16a molecules with an approximate 17 nm intra-doublet distance.
• NK cell activation led to increased CD16a density in synaptic regions.
• The study achieved the highest spatial resolution to date for CD16a imaging.

Conclusions:

• CD16a organization, including dimerization, within the immune synapse may influence ADCC activity.
• MINFLUX nanoscopy offers a powerful tool to study NK cell activation mechanisms at the molecular level.