Cutting edge: lectin-like transcript 1 is a ligand for the CD161 receptor

Area of Science:

• Immunology
• Cell Biology

Background:

• Human NK cells, T cells, and NKT cells express the CD161 receptor (NKR-P1A), a C-type lectin with an unclear function.
• Unlike rodents with multiple NKR-P1 genes, the signaling pathways of the single human NKR-P1A remain poorly understood.

Purpose of the Study:

• To identify the functional ligand for the human CD161 receptor.
• To elucidate the role of the CD161 receptor in regulating immune cell functions.

Main Methods:

• Investigated the interaction between CD161 and its potential ligand, LLT1.
• Assessed the impact of CD161/LLT1 engagement on NK cell cytotoxicity and IFN-gamma secretion.
• Examined the effect of LLT1/CD161 interaction on T cell IFN-gamma production in conjunction with TCR signaling.

Main Results:

• Identified lectin-like transcript 1 (LLT1) as a specific ligand for the CD161 receptor.
• Engagement of CD161 on NK cells by LLT1 on target cells suppressed NK cell cytotoxicity and IFN-gamma secretion.
• LLT1/CD161 interaction, combined with TCR signaling, augmented IFN-gamma production in T cells.

Conclusions:

• Established LLT1 as a functional ligand for CD161, revealing a novel receptor-ligand pair.
• Demonstrated that the LLT1/CD161 interaction differentially modulates NK and T cell functions.
• The findings provide new insights into the regulation of adaptive and innate immune responses by CD161 signaling.