ULBP6/RAET1L is an additional human NKG2D ligand

• Published in: European journal of immunology Vol. 39; no. 11; pp. 3207 - 3216
• Main Authors: Eagle, Robert A, Traherne, James A, Hair, James R, Jafferji, Insiya, Trowsdale, John
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley-VCH Verlag 01.11.2009; WILEY‐VCH Verlag
• Subjects: Blotting, Western; Gene Expression Profiling; GPI-Linked Proteins; Humans; Immune evasion; Infectious diseases; Innate immunity; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - immunology; Killer Cells, Natural - immunology; Lymphocyte Activation - immunology; Microscopy, Confocal; NK cells; NK‐cell ligands; Reverse Transcriptase Polymerase Chain Reaction
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200939502

To date five ULBP/RAET (UL16-binding protein, also known as retinoic acid early transcript) genes, encoded on human chromosome 6q24.2-q25.3, have been shown to encode ligands of the activating immunoreceptor NKG2D. Here, we show that a sixth gene, ULBP6/RAET1L, is a polymorphic locus that expresses a functional transcript. ULBP6 had a more restricted expression profile in cell lines and primary human tissues than other NKG2D ligands, but expression was detected in several human papillomavirus-positive cervical carcinoma cell lines and was inducible on infection with human CMV. ULBP6 bound to recombinant NKG2D as well as the human CMV immune evasion molecule UL16. By confocal microscopy we show that UL16 retains ULBP6 inside the cell, preventing it from reaching the cell surface. Expression of ULBP6 on target cells induced a significant increase in NK-cell killing. Comparison of ULBP6 with ULBP4 and ULBP5 indicated that differences in recombinant NKG2D binding correlated with differences in NK-cell activation.