A5075566685- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- Ubiquitin and proteasome pathways
- Complement system in diseases
- Galectins and Cancer Biology
- Cell Adhesion Molecules Research
- Platelet Disorders and Treatments
- vaccines and immunoinformatics approaches
- Protein Hydrolysis and Bioactive Peptides
- Blood groups and transfusion
- Photoreceptor and optogenetics research
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- Evolution and Genetic Dynamics
- Lysosomal Storage Disorders Research
- Transgenic Plants and Applications
- Genetics, Aging, and Longevity in Model Organisms
- Advanced Electron Microscopy Techniques and Applications
- Carbohydrate Chemistry and Synthesis
- Biopolymer Synthesis and Applications
- Cell death mechanisms and regulation
- Graphene and Nanomaterials Applications
Tokyo University of Science
1998-2023
National Institute of Advanced Industrial Science and Technology
2007-2010
Kyushu University
2008
Tohoku University
2008
University of Tsukuba
2008
Tokyo Medical and Dental University
2003
Center of Molecular Immunology (Cuba)
2002
University of Colorado Health
1995-1998
University of Iowa
1997
University of Colorado Denver
1995
Human complement receptors type 1 (hCR1;CD35) and 2 (hCR2;CD21) are expressed on B lymphocytes at specific stages during differentiation activation. These play critical roles in the immune response to T-dependent Ags addition germinal center formation. Expression of both hCR2 hCR1 is decreased patients with systemic lupus erythematosus (SLE). We have studied expression mouse CR2 CR1 normal populations BALB/c mice. Our results demonstrate that these state closely parallels hCR2. During bone...
Abstract B7 homologous protein (B7h)/B7-related 1 (B7RP-1) is a new member of the family costimulatory molecules that specifically interacts with inducible costimulator (ICOS) expressed on activated T cells. Collagen type II (CII)-induced arthritis (CIA) an experimental model has been used to dissect pathogenesis human rheumatoid arthritis. In this study, we have investigated effect neutralizing anti-B7h mAb development and disease progression CIA. Administration significantly ameliorated as...
beta1,3-N-acetylglucosaminyltransferase 2 (beta3GnT2) is a polylactosamine synthase that synthesizes backbone structure of carbohydrate structures onto glycoproteins. Here we generated beta3GnT2-deficient (beta3GnT2(-/-)) mice and showed on N-glycans was markedly reduced in their immunological tissues. In WT mice, present CD28 CD19, both known immune costimulatory molecules. However, levels these molecules were beta3GnT2(-/-) mice. T cells lacking more sensitive to the induction...
Abstract A recombinant soluble form of the mouse membrane complement inhibitor Crry (complement receptor-related gene y) fused to IgG1 hinge, CH2, and CH3 domains has been created designated Crry-Ig. used because, similar human CR1, it demonstrates decay-accelerating activity for both classical alternative pathways as well cofactor factor I-mediated cleavage C3b C4b. The isotype was incorporated because is a noncomplement-activating and, when Crry, results in that should not be recognized...
The mammalian circadian clock proteins undergo a daily cycle of accumulation followed by phosphorylation and degradation. mechanism which degradation has not been fully understood. Circadian protein PERIOD2 (PER2) is shown to be the potential target F-box beta-TrCP1, component ubiquitin E3 ligase. Here, we show that beta-TrCP2 as well beta-TrCP1 PER2 in vitro. We also identified beta-TrCP binding site (m2) being recognized both beta-TrCP2. Luciferase-PER2 fusion system revealed m2 was...
Abstract Activation of the complement cascade and ligation C3 receptors on B cells represent an important bridge between innate Ag-specific acquired immunity. We show here that cross-linking mouse CD21 (complement receptor type 2, CR2, C3d receptor) CD35 1, CR1, C3b/C4b or co-cross-linking CD21/CD35 surface IgM rapidly up-regulates both B7-1 B7-2 expression murine resting splenic cells. CD21/CD35-mediated up-regulation is observed within 14 h, while other stimuli up-regulate only but not at...
Abstract Recent studies have shown that complement receptors play important roles in both T‐dependent and T‐independent B lymphocyte responses to low doses of antigen (Ag) vivo. Complement activation by either the classical or alternative pathway results covalent binding C3 molecules Ag forms ligate type 1 (CR1) 2 (CR2). We hypothesized C3‐bound might cross‐link CR2 and/or CR1 with surface (s)IgM alter signal would be transduced through sIgM alone. One result altered could rescue lymphocytes...
New Zealand Black (NZB) mice spontaneously develop autoimmune disease, usually characterized by an hemolytic anemia, and NZB genes are essential for a severe systemic lupus-like disease in (NZB x NZW)F1 mice. We have found that resting B cells from demonstrate pronounced defect, compared with five normal strains, apoptosis induction after cross-linking anti-IgM Abs. In contrast, spontaneous of culture was similar to strains. young SM/J)F1 underwent normally, indicating the defect is...
In a previous study, we demonstrated that β1,3- N -acetylglucosaminyltransferase 5 ( B3gnt5 ) is lactotriaosylceramide (Lc 3 Cer) synthase synthesizes precursor structure for lacto/neolacto-series glycosphingolipids (GSLs) in vitro experiments. Here, generated -deficient −/− mice to investigate the vivo biological functions of GSLs. biochemical analyses, GSLs were confirmed be absent and no Lc Cer activity was detected tissues these mice. These results demonstrate β3GnT5 sole enzyme...
Abstract Chimeric mice were prepared from embryonic stem cells transfected with IgH genes as transgenes and RAG-2-deficient blastocysts for the purpose of identifying cis-acting elements responsible induction somatic hypermutation. Among three transgene constructs used, VH promoter, rearranged VH-D-JH, an intron enhancer/matrix attachment region, human Cμ common to all, but 3′-untranslated region in each construct was different. After immunization a T cell-dependent Ag, distribution...
We have applied our advanced computational and experimental methodologies to investigate the complex structure binding mechanism of a modified Wilms' Tumor 1 (mWT1) protein epitope understudied Asian-dominant allele HLA-A*24:02 (HLA-A24) in aqueous solution. developed multicanonical molecular dynamics (McMD)-based dynamic docking method analyze pathway mechanism, which we verified by comparing highest probability structures from simulation with experimentally solved x-ray crystal structure....
Medullary thymic epithelial cells (mTECs), which express a wide range of tissue-restricted Ags (TRAs), contribute to the establishment self-tolerance by eliminating autoreactive T and/or inducing regulatory cells. Aire controls diverse set TRAs within Aire-expressing employing various transcriptional pathways. As has profound effect on transcriptomes mTECs, including not only at single-cell but also population level, we suspected that (Aire+ mTECs) might control cellular composition...
Ubiquitination is a process that dictates the lifespan of major histocompatibility complex class II (MHC II)/peptide complexes on antigen-presenting cells. This tightly controlled by levels ubiquitin ligases, and disruptions in turnover MHC can lead to improper development CD4+ T cells within thymus hinder formation regulatory peripheral tissue. To investigate underlying mechanisms, we utilized dendritic lacking Membrane-associated RING-CH (MARCH) I ligase. We discovered overexpression MARCH...
Class II MHC can take loosely bound peptides conformations, which generated in the recycling endosomes or cell surface, that are recognized by autoimmune T cells. DM converts complexes to tightly complexes; crystal structure advocated form of generate novel threshold for peptide binding creating a hydrogen bond inside groove, intermediate complex. We used soluble I‐A k and two differ their length as model system detect such floating peptides. Fluorescein quenching study provided remarkable...
Event Abstract Back to Ubiquitin ligase MARCH I involves peptide discrimination for MHC II complex Yuko Kozono1, Ryuma Tanizawa1, Yuji C. Sasaki2, Satoshi Ishido3, Osami Kanagawa4 and Haruo Kozono1* 1 Tokyo University of Science, Japan 2 The Univercity Tokyo, 3 RIKEN, RCAI, 4 Akashi City Hospital, We examined whether ubiquitin distinguish the structural fluctuation MHC/peptide complexes. Ubiquitination is necessary intracellular transport from cell membrane acidic endosomes vice versa....