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The Journal of Immunology, 2002, 169: 4079-4083.
Copyright © 2002 by The American Association of Immunologists

Cutting Edge

Cutting Edge: Murine UL16-Binding Protein-Like Transcript 1: A Newly Described Transcript Encoding a High-Affinity Ligand for Murine NKG2D1

Leonidas N. Carayannopoulos*, Olga V. Naidenko{dagger}, Daved H. Fremont{dagger} and Wayne M. Yokoyama2,{ddagger}

* Division of Pulmonary and Critical Care Medicine, {dagger} Department of Pathology and Immunology, and {ddagger} Division of Rheumatology and Howard Hughes Medical Institute, Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO 63110

Murine NKG2D is known to recognize H60 and five RAE1 variants. The human homologue recognizes both inducible MHC class I chain-related gene and constitutive (UL16-binding protein (ULBP)) ligands. Widely expressed, the latter are thought to mark transformed or infected cells for destruction by NK cells in the context of down-regulated cell surface class I (i.e., the "missing self"-response). Unlike MIC and ULBP however, mRNA for the murine ligands appears only in very limited contexts in the mature animal. In this study, we describe a NKG2D ligand termed "murine ULBP-like transcript 1 (MULT1) whose mRNA appears to be widely expressed in adult parenchyma. This molecule possesses MHC class I-like {alpha}1 and {alpha}2 domains as well as a large cytoplasmic domain. Recombinant MULT1 binds NKG2D with relatively high affinity (KD {approx} 6 nM) and low koff (~0.006s-1). Expression of MULT1 by normally resistant RMA cells results in their susceptibility to lysis by C57BL/6 splenocytes.




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