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 - Institute for Virus Research
Cell Regulation
Viral Oncology
The universe of antigens recognized by the immune system has recently been expanded to include not only protein antigens but also lipid antigens. The Lipid-specific T cell response is mediated primarily by a novel lineage of antigen-presenting molecules, CD1, that exhibits an outstanding ability to bind lipid antigens and present them to specific T cells. By orchestrating immunological, cell biological, and biochemical approaches, our laboratory aims to establish the molecular and cellular basis for lipid antigen presentation and T cell activation, hoping to contribute to accurate diagnosis of cancer and microbial infection and develop a new type of lipid-based vaccines. We encourage young investigators interested in our research endeavors to join us regardless of their educational backgrounds.

  Masahiko Sugita, M.D., Ph.D.
Research and Education
Rapid progress in molecular biology in the 1980s resulted in elucidation of a molecular basis for the protein antigen-specific immunity. Milestone discoveries such as X-ray crystallographic visualization of peptide-MHC interactions and the diversity of T-cell receptors generated by gene rearrangement convinced most immunologists with excitement that the molecular basis for “antigen specificity”, a most salient feature of our immune system, had been fully disclosed. While sharing excitement as one among members of the immunology community, I was personally puzzled by a naive question that came up to me after clinical practice. “Does the universe of antigens recognized by the immune system only include proteins?” Glycan-specific immune responses are elicited following pneumococcal infection. Campylobacter infection often induces immune responses directed against glycolipids. Autoantibodies against double-strand DNA are detected in patients with systemic lupus erythematosus. These clinical observations provide evidence for the yet unappreciated ability of the immune system to specifically recognize non-protein antigens that include sugars, lipids, and nucleic acids. Our laboratory now aims to unravel a molecular and cellular basis for the lipid-specific immune response and to develop lipid-based vaccines against cancer and microbial infection. Young investigators sharing enthusiasm with us would join in our journey to these goals.

Cell Regulation
Institute for Virus Research
Professor Masahiko Sugita

Isamu Matsunaga
TEL +81-75-751-4028
FAX +81-75-752-3232
In contrast to MHC molecules that present protein antigens to T cells, CD1 molecules bind lipid antigens and present them to T cells. These two pathways function cooperatively to support host defense.
Electron micrographs of dendritic cells (left) that primarily function to mediate lipid antigen presentation and dendritic cell lysosomes (right) where lipid antigen loading onto CD1 molecules occurs.
Guinea pigs used for our study of CD1 (upper panel) and CD1-positive cells in CD1 transgenic mice (lower panel, stained in brown).
A group photo of our laboratory
Recent Publications
1. Nakao, H., et al. (2009) Mycolyltransferase from Mycobacterium leprae excludes mycolate-containing glycolipid substrates. J. Biochem. 146:659-665.
2. Otsuka, A., et al. (2008) Trehalose dimycolate elicits eosinophilic skin hypersensitivity in mycobacteria-infected guinea pigs. J. Immunol. 181:8528-8533.
3. Matsunaga, I., et al. (2008) Mycoyltransferase-mediated glycolipid exchange in Mycobacteria. J. Biol. Chem. 283: 28835-28841.
4. Matsumoto, Y., et al. (2008) Guillain-Barre syndrome-associated IgG responses to gangliosides are generated independently of CD1 function in mce. J. Immunol. 181: 39-43.
5. Hava, DL., et al. (2008) Evasion of peptide, but not lipid antigen presentation, through pathogen-induced dendritic cell maturation. Proc. Natl. Acad. Sci. USA. 105: 11281-11286.