Pattern Recognition by TREM-2: Binding of Anionic Ligands

• Published in: The Journal of immunology (1950) 2003-07, Vol.171 (2), p.594-599
• Main Authors: Daws, Michael R, Sullam, Paul M, Niemi, Erene C, Chen, Thomas T, Tchao, Nadia K, Seaman, William E
• Format: Article
• Language: English
• Subjects: Animals; Anions; Astrocytoma - metabolism; Astrocytoma - microbiology; Bacterial Adhesion - drug effects; Bacterial Adhesion - genetics; Bacterial Adhesion - immunology; Binding, Competitive - genetics; Binding, Competitive - immunology; Dextran Sulfate - pharmacology; Gram-Negative Bacteria - physiology; Gram-Positive Bacteria - physiology; Humans; Immunoglobulin Fc Fragments - genetics; Immunoglobulin Fc Fragments - metabolism; Jurkat Cells; Leukemia P388; Ligands; Lipopolysaccharides - pharmacology; Mice; Peptidoglycan - pharmacology; Protein Binding - drug effects; Protein Binding - genetics; Protein Binding - immunology; Receptors, Immunologic - biosynthesis; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; Receptors, Immunologic - physiology; Recombinant Fusion Proteins - antagonists & inhibitors; Recombinant Fusion Proteins - metabolism; Solubility; Teichoic Acids - pharmacology; Transfection; Tumor Cells, Cultured
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.171.2.594

We recently described the cloning of murine triggering receptor expressed by myeloid cells (TREM) 2, a single Ig domain DNAX adaptor protein 12-associated receptor expressed by cells of the myeloid lineage. In this study, we describe the identification of ligands for TREM-2 on both bacteria and mammalian cells. First, by using a TREM-2A/IgG1-Fc fusion protein, we demonstrate specific binding to a number of Gram-negative and Gram-positive bacteria and to yeast. Furthermore, we show that fluorescently labeled Escherichia coli and Staphylococcus aureus bind specifically to TREM-2-transfected cells. The binding of TREM-2A/Ig fusion protein to E. coli can be inhibited by the bacterial products LPS, lipoteichoic acid, and peptidoglycan. Additionally, binding can be inhibited by a number of other anionic carbohydrate molecules, including dextran sulfate, suggesting that ligand recognition is based partly on charge. Using a sensitive reporter assay, we demonstrate activation of a TREM-2A/CD3zeta chimeric receptor by both bacteria and dextran sulfate. Finally, we demonstrate binding of TREM-2A/Ig fusion to a series of human astrocytoma lines but not to a variety of other cell lines. The binding to astrocytomas, like binding to bacteria, is inhibited by anionic bacterial products, suggesting either a similar charge-based ligand recognition method or overlapping binding sites for recognition of self- and pathogen-expressed ligands.