Intercellular transfer and supramolecular organization of human leukocyte antigen C at inhibitory natural killer cell immune synapses

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• Natural killer (NK) cells are crucial for innate immunity, recognizing and eliminating target cells.
• Immune synapses are specialized cell-cell junctions formed between immune cells.
• Human leukocyte antigen (HLA)-C molecules are key ligands for inhibitory NK cell receptors.

Purpose of the Study:

• To investigate the unexpected intercellular transfer of HLA-C from target cells to NK cells.
• To elucidate the mechanisms and dependencies of HLA-C transfer at the NK cell immune synapse.

Main Methods:

• Live-cell time-lapse laser scanning confocal microscopy.
• NK cell transfectants expressing killer Ig-like receptors (KIRs).
• Assessment of ATP and actin cytoskeleton dependence.

Main Results:

• Intercellular transfer of HLA-C from target cells to NK cells was observed.
• HLA-C transfer was dependent on NK receptor recognition (e.g., KIR2DL1 binding to HLA-Cw6 or -Cw4).
• Vesicular transport of HLA-C into NK cells was visualized, requiring NK cell ATP but not actin polymerization.

Conclusions:

• NK cell immune synapses facilitate the active, vesicular transfer of target cell HLA-C into NK cells.
• This transfer mechanism is distinct from simple HLA-C clustering and relies on NK cell-intrinsic processes.
• Understanding HLA-C transfer provides novel insights into NK cell regulation and immune synapse function.