ULBP6/RAET1L is an additional human NKG2D ligand

Area of Science:

• Immunology
• Molecular Biology
• Genetics

Background:

• Five ULBP/RAET genes encode ligands for the activating immunoreceptor NKG2D.
• These genes are located on human chromosome 6q24.2-q25.3.

Purpose of the Study:

• To investigate the function and expression of a sixth ULBP gene, ULBP6/RAET1L.
• To determine ULBP6's interaction with NKG2D and the human CMV immune evasion molecule UL16.

Main Methods:

• Analysis of ULBP6 gene expression in cell lines and primary tissues.
• Binding assays with recombinant NKG2D and UL16.
• Confocal microscopy to visualize ULBP6 localization.
• Assessment of NK-cell killing upon ULBP6 expression.

Main Results:

• ULBP6 is a polymorphic locus expressing a functional transcript with a restricted expression profile.
• ULBP6 expression was detected in human papillomavirus-positive cervical carcinoma cell lines and induced by human CMV infection.
• ULBP6 binds NKG2D and UL16; UL16 retains ULBP6 intracellularly.
• ULBP6 expression significantly increased NK-cell killing, with binding differences correlating to NK-cell activation.

Conclusions:

• ULBP6 is a novel NKG2D ligand with a distinct expression pattern.
• The human CMV UL16 molecule can sequester ULBP6 intracellularly.
• ULBP6 plays a role in NK-cell mediated immunity and viral immune evasion.