Lysosomal Glycosphingolipid Recognition by NKT Cells

• Published in: Science (American Association for the Advancement of Science) Vol. 306; no. 5702; pp. 1786 - 1789
• Main Authors: Zhou, Dapeng, Mattner, Jochen, Cantu, Carlos, Schrantz, Nicolas, Yin, Ning, Gao, Ying, Sagiv, Yuval, Hudspeth, Kelly, Wu, Yun-Ping, Yamashita, Tadashi, Teneberg, Susann, Wang, Dacheng, Proia, Richard L., Levery, Steven B., Savage, Paul B., Teyton, Luc, Bendelac, Albert
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 03.12.2004; The American Association for the Advancement of Science
• Subjects: alpha-beta; Animals; Antigen; Antigen Presentation; Antigens; Antigens, CD1 - immunology; Antigens, CD1 - metabolism; Antigens, CD1d; Autoimmunity; beta-N-Acetylhexosaminidase; beta-N-Acetylhexosaminidases - genetics; beta-N-Acetylhexosaminidases - metabolism; Biological and medical sciences; CD1; Cell Line; Cell Line, Tumor; Cells; Cells, Cultured; chemistry; Cultured; Dendritic Cells; Dendritic Cells - immunology; Enzymes; Feedback (Response); Fundamental and applied biological sciences. Psychology; Fundamental immunology; Galactosyltransferases; Galactosyltransferases - genetics; Galactosyltransferases - metabolism; genetics; Globosides; Globosides - chemistry; Globosides - immunology; Globosides - metabolism; Glycolipids; Glycosphingolipids; Human subjects; Humans; Hybridomas; Immunobiology; immunology; Inbred C57BL; Infection; Infection - immunology; Killer Cells; Killer Cells, Natural - immunology; Lectins; Ligands; Lipids; Lymphocyte Activation; Lymphocyte Count; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Lysosomes; Lysosomes - metabolism; Medical and Health Sciences; Medicin och hälsovetenskap; metabolism; Mice; Mice, Inbred C57BL; Natural; Natural killer T cells; Neoplasms; Neoplasms - immunology; Plant Lectins; Plant Lectins - immunology; Rats; Receptors; Receptors, Antigen, T-Cell, alpha-beta - immunology; Rodents; Saposins; Saposins - metabolism; T cell antigen receptors; T cell receptors; T cells; T lymphocytes; T-Cell; T-Lymphocyte Subsets; T-Lymphocyte Subsets - immunology; Tumor; United States; Natural killer cell; Human; Vertebrata; Mammalia; Mouse; Rodentia; Lysosome; Sphingoglycolipid; Lipids
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.1103440

NKT cells represent a distinct lineage of T cells that coexpress a conserved αβ T cell receptor (TCR) and natural killer (NK) receptors. Although the TCR of NKT cells is characteristically autoreactive to CD1d, a lipid-presenting molecule, endogenous ligands for these cells have not been identified. We show that a lysosomal glycosphingolipid of previously unknown function, isoglobotrihexosylceramide (iGb3), is recognized both by mouse and human NKT cells. Impaired generation of lysosomal iGb3 in mice lacking β-hexosaminidase b results in severe NKT cell deficiency, suggesting that this lipid also mediates development of NKT cells in the mouse. We suggest that expression of iGb3 in peripheral tissues may be involved in controlling NKT cell responses to infections and malignancy and in autoimmunity.