Natural Ligand of Mouse CD1d1: Cellular Glycosylphosphatidylinositol

• Published in: Science (American Association for the Advancement of Science) Vol. 279; no. 5356; pp. 1541 - 1544
• Main Authors: Joyce, Sebastian, Woods, Amina S., Yewdell, Jonathan W., Bennink, Jack R., de Silva, A. Dharshan, Boesteanu, Alina, Balk, Steven P., Cotter, Robert J., Brutkiewicz, Randy R.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 06-03-1998; American Association for the Advancement of Science
• Subjects: Animals; Antibodies, immunoglobulins; Antigens, CD1 - chemistry; Antigens, CD1 - isolation & purification; Antigens, CD1 - metabolism; Binding Sites; Biological and medical sciences; Cations; Filtration; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Glycosylphosphatidylinositols - chemistry; Glycosylphosphatidylinositols - metabolism; HLA antigens; Immune response; Immune response regulation; Ions; Ligands; Mass spectra; Mass Spectrometry; Mice; Molecular immunology; Molecules; Natural killer T cells; Physiological aspects; Regulation; Solubility; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Structure; Sulfates; T cells; T lymphocytes; T-Lymphocyte Subsets - immunology; Natural killer cell; Ligand binding; Vertebrata; Glycophospholipid; Mammalia; Mouse; Rodentia; T-Lymphocyte; Molecular interaction; Binding site; Glycosylphosphatidylinositol
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.279.5356.1541

Mouse CD1d1, a member of the CD1 family of evolutionarily conserved major histocompatibility antigen-like molecules, controls the differentiation and function of a T lymphocyte subset, NK1$^+$ natural T cells, proposed to regulate immune responses. The CD1d1 crystal structure revealed a large hydrophobic binding site occupied by a ligand of unknown chemical nature. Mass spectrometry and metabolic radiolabeling were used to identify cellular glycosylphosphatidylinositol as a major natural ligand of CD1d1. CD1d1 bound glycosylphosphatidylinositol through its phosphatidylinositol aspect with high affinity. Glycosylphosphatidylinositol or another glycolipid could be a candidate natural ligand for CD1d1-restricted T cells.