Educational Activities

Graduate school:Bio-Medicine, Drug Discovery, Bioscience Analytical Instruments

Research Activities

Recognition in Innate Immunity

The bodies of vertebrates, including us humans, are protected from invading pathogens and arising cancer by immune system. The immune system in the vertebrates is comprised of innate and adaptive immunity.


Our group focuses on the recognition by innate immune cells, which include natural killer (NK) cells and dendritic cells (DC). The innate immune cells use two kinds of receptors: inhibitory receptors, which recognize structures expressed in normal self, and activating receptors, which recognize structures found in pathogens and abnormal cells.


Recognition of MHC class I ligands by NK cell receptors

NK cells express inhibitory receptors for MHC class I molecules, which are ubiquitously expressed throughout our bodies and function as markers for self. We succeeded in identifying the binding sites on MHC class I for two of such NK cell receptors: Ly49A and CD94/NKG2. Surprisingly, despite their homologous structure, Ly49A and CD94/NKG2 bind totally different site of respective MHC class I ligands.


Ligands and function of the inhibitory NK cell receptor KLRG1.

We recently identified classical cadherins, which participate in cell-cell adherion, as the ligands for KLRG1, which is a receptor expressed on subsets of NK cells and T cells. Our findings indicate that in addition to MHC class I molecules, which have been shown to function as self markers, NK cells use adhesion molecules abundantly expressed in our bodies as markers of normal self. We are currently studying in vivo function of this receptor.


Inhibitory lectin receptors expressed on dendritic cells.

Dendritic cells (DC) are professional antigen presenting cells, which play essential role in initiating and suppressing T cell-mediated immunity. While activating receptors on DC, also called as pattern recognition receptors, have been extensively studied, inhibitory receptors on DC are poorly characterized. We are studying ligands and function of DCIR family of inhibitory lectin receptors, which may recognize carbohydrate ligands of self to regulate function of DC.

Literature

1) Matsumoto N., Ribaudo R.K. , Abastado J.-P., Margulies D. H., and Yokoyama W. M. "The lectin-like NK cell receptor Ly-49A recognizes a carbohydrate-independent epitope on its MHC class I ligand" Immunity 8: 245-254 (1998)
2) Matsumoto N., Mitsuki M., Tajima K., Yokoyama W.M., and Yamamoto K. "The functional binding site for the C-type lectin-like NK cell receptor Ly49A spans three domains of its MHC class I ligand." J. Exp. Med. 193, 147-157 (2001)
3) Wada H., Matsumoto N., Maenaka K., Suzuki K., and Yamamoto K. "The inhibitory NK cell receptor CD94/NKG2A and the activating receptor CD94/NKG2C Bind the top of HLA-E through mostly shared but partly distinct sets of HLA-E Residues" Eur. J. Immunol. 34, 81-90 (2004).
4) Ito M., Maruyama T., Saito N., Koganei S., Yamamoto K., and Matsumoto N. "Killer cell lectin-like receptor G1 binds three members of the classical cadherin family to inhibit NK cell cytotoxicity" J. Exp. Med. 203, 289-295 (2006)

Other Activities

Japanese Society of Immunology
Japanese Society of Biochemistry
Japanese Society of Glycosciences
Society of Natural Immunity