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Book ; Conference proceedings: IMMUNOGENETICS

Sasazuki, Takehiko

ITS APPLICATION TO CLINICAL MEDICINE ; (PROC. OF THE INTERNAT. SYMPOSIUM ON IMMUNOGENETICS ... HELD IN TOKYO, JAPAN, AUG. 17 - 19, 1983)

1984

Author's details	ED. BY TAKEHIKO SASAZUKI
Keywords	IMMUNOGENETICS / CONGRESSES ; Immungenetik
Subject	Immunogenetik
Size	XVII, 308 S. : ILL., GRAPH. DARST.
Publisher	ACADEMIC PR
Publishing place	TOKYO (U.A.)
Document type	Book ; Conference proceedings
HBZ-ID	HT002745379
ISBN	0-12-619420-3 ; 978-0-12-619420-3
Database	Catalogue ZB MED Medicine, Health

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Article ; Online: Abrogation of self-tolerance by misfolded self-antigens complexed with MHC class II molecules.

Jin, Hui / Kishida, Kazuki / Arase, Noriko / Matsuoka, Sumiko / Nakai, Wataru / Kohyama, Masako / Suenaga, Tadahiro / Yamamoto, Ken / Sasazuki, Takehiko / Arase, Hisashi

Science advances

2022 Volume 8, Issue 9, Page(s) eabj9867

Abstract: Specific MHC class II alleles are strongly associated with susceptibility to various autoimmune diseases. Although the primary function of MHC class II molecules is to present peptides to helper T cells, MHC class II molecules also function like a ... ...

Abstract	Specific MHC class II alleles are strongly associated with susceptibility to various autoimmune diseases. Although the primary function of MHC class II molecules is to present peptides to helper T cells, MHC class II molecules also function like a chaperone to transport misfolded intracellular proteins to the cell surface. In this study, we found that autoantibodies in patients with Graves' disease preferentially recognize thyroid-stimulating hormone receptor (TSHR) complexed with MHC class II molecules of Graves' disease risk alleles, suggesting that the aberrant TSHR transported by MHC class II molecules is the target of autoantibodies produced in Graves' disease. Mice injected with cells expressing mouse TSHR complexed with MHC class II molecules, but not TSHR alone, produced anti-TSHR autoantibodies. These findings suggested that aberrant self-antigens transported by MHC class II molecules exhibit antigenic properties that differ from normal self-antigens and abrogate self-tolerance, providing a novel mechanism for autoimmunity.
Language	English
Publishing date	2022-03-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.abj9867
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Book: Hatsugan no bunshi kikō to bōgyo

Sasazuki, Takehiko

(Gan kenkyū no ima ; 1)

2006

Title variant	Molecular carcinogenesis
Author's details	Sasazuki Takehiko, Noda Tetsuo hen
Series title	Gan kenkyū no ima ; 1
MeSH term(s)	Neoplasms/physiopathology
Language	Japanese
Size	xi, 197 p. :, ill.
Edition	Shohan.
Publisher	Tōkyō Daigaku Shuppankai
Publishing place	Tōkyō
Document type	Book
ISBN	9784130642415 ; 4130642413
Database	Catalogue of the US National Library of Medicine (NLM)

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Article ; Online: Gene Map of the HLA Region, Graves' Disease and Hashimoto Thyroiditis, and Hematopoietic Stem Cell Transplantation.

Sasazuki, Takehiko / Inoko, Hidetoshi / Morishima, Satoko / Morishima, Yasuo

Advances in immunology

2016 Volume 129, Page(s) 175–249

Abstract: The human leukocyte antigen (HLA) genomic region spanning about 4 Mb is the most gene dense and the polymorphic stretches in the human genome. A total of the 269 loci were identified, including 145 protein coding genes mostly important for immunity and ... ...

Abstract	The human leukocyte antigen (HLA) genomic region spanning about 4 Mb is the most gene dense and the polymorphic stretches in the human genome. A total of the 269 loci were identified, including 145 protein coding genes mostly important for immunity and 50 noncoding RNAs (ncRNAs). Biological function of these ncRNAs remains unknown, becoming hot spot in the studies of HLA-associated diseases. The genomic diversity analysis in the HLA region facilitated by next-generation sequencing will pave the way to molecular understanding of linkage disequilibrium structure, population diversity, histocompatibility in transplantation, and associations with autoimmune diseases. The 4-digit DNA genotyping of HLA for six HLA loci, HLA-A through DP, in the patients with Graves' disease (GD) and Hashimoto thyroiditis (HT) identified six susceptible and three resistant HLA alleles. Their epistatic interactions in controlling the development of these diseases are shown. Four susceptible and one resistant HLA alleles are shared by GD and HT. Two HLA alleles associated with GD or HT control the titers of autoantibodies to thyroid antigens. All these observations led us to propose a new model for the development of GD and HT. Hematopoietic stem cell transplantation from unrelated donor (UR-HSCT) provides a natural experiment to elucidate the role of allogenic HLA molecules in immune response. Large cohort studies using HLA allele and clinical outcome data have elucidated that (1) HLA locus, allele, and haplotype mismatches between donor and patient, (2) specific amino acid substitution at specific positions of HLA molecules, and (3) ethnic background are all responsible for the immunological events related to UR-HSCT including acute graft-versus-host disease (GVHD), chronic GVHD, graft-versus-leukemia (GvL) effect, and graft failure.
MeSH term(s)	Alleles ; Autoantibodies/blood ; Autoantibodies/genetics ; Autoantibodies/immunology ; Chromosome Mapping ; Epistasis, Genetic ; Genetic Predisposition to Disease ; Genetic Variation ; Graft vs Host Disease/genetics ; Graft vs Leukemia Effect/genetics ; Graft vs Leukemia Effect/immunology ; Graves Disease/genetics ; Haplotypes ; Hashimoto Disease/genetics ; Hematopoietic Stem Cell Transplantation ; High-Throughput Nucleotide Sequencing ; Histocompatibility Antigens Class I/genetics ; Histocompatibility Antigens Class II/genetics ; Humans
Chemical Substances	Autoantibodies ; Histocompatibility Antigens Class I ; Histocompatibility Antigens Class II
Language	English
Publishing date	2016
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80226-8
ISSN	1557-8445 ; 0065-2776
ISSN (online)	1557-8445
ISSN	0065-2776
DOI	10.1016/bs.ai.2015.08.003
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Ud II Zs.191: Show issues

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Article ; Online: Contributions of the N-terminal flanking residues of an antigenic peptide from the Japanese cedar pollen allergen Cry j 1 to the T-cell activation by HLA-DP5.

Kusano, Seisuke / Ueda, Sho / Oryoji, Daisuke / Toyoumi, Aya / Hashimoto-Tane, Akiko / Kishi, Hiroyuki / Hamana, Hiroshi / Muraguchi, Atsushi / Jin, Hui / Arase, Hisashi / Miyadera, Hiroko / Kishikawa, Reiko / Yoshikai, Yasunobu / Yamada, Hisakata / Yamamoto, Ken / Nishimura, Yasuharu / Saito, Takashi / Sasazuki, Takehiko / Yokoyama, Shigeyuki

International immunology

2023 Volume 35, Issue 9, Page(s) 447–458

Abstract: Cry j 1 is a major allergen present in Japanese cedar (Cryptomeria japonica) pollens. Peptides with the core sequence of KVTVAFNQF from Cry j 1 ('pCj1') bind to HLA-DP5 and activate Th2 cells. In this study, we noticed that Ser and Lys at positions -2 ... ...

Abstract	Cry j 1 is a major allergen present in Japanese cedar (Cryptomeria japonica) pollens. Peptides with the core sequence of KVTVAFNQF from Cry j 1 ('pCj1') bind to HLA-DP5 and activate Th2 cells. In this study, we noticed that Ser and Lys at positions -2 and -3, respectively, in the N-terminal flanking (NF) region to pCj1 are conserved well in HLA-DP5-binding allergen peptides. A competitive binding assay showed that the double mutation of Ser(-2) and Lys(-3) to Glu [S(P-2)E/K(P-3)E] in a 13-residue Cry j 1 peptide (NF-pCj1) decreased its affinity for HLA-DP5 by about 2-fold. Similarly, this double mutation reduced, by about 2-fold, the amount of NF-pCj1 presented on the surface of mouse antigen-presenting dendritic cell line 1 (mDC1) cells stably expressing HLA-DP5. We established NF-pCj1-specific and HLA-DP5-restricted CD4+ T-cell clones from HLA-DP5 positive cedar pollinosis (CP) patients, and analyzed their IL-2 production due to the activation of mouse TG40 cells expressing the cloned T-cell receptor by the NF-pCj1-presenting mDC1 cells. The T-cell activation was actually decreased by the S(P-2)E/K(P-3)E mutation, corresponding to the reduction in the peptide presentation by this mutation. In contrast, the affinity of NF-pCj1·HLA-DP5 for the T-cell receptor was not affected by the S(P-2)E/K(P-3)E mutation, as analyzed by surface plasmon resonance. Considering the positional and side-chain differences of these NF residues from previously reported T-cell activating sequences, the mechanisms of enhanced T-cell activation by Ser(-2) and Lys(-3) of NF-pCj1 may be novel.
MeSH term(s)	Animals ; Mice ; Allergens ; Cryptomeria/chemistry ; Antigens, Plant ; Plant Proteins/genetics ; Plant Proteins/analysis ; Plant Proteins/chemistry ; Pollen ; Peptides ; Receptors, Antigen, T-Cell
Chemical Substances	Allergens ; Antigens, Plant ; Plant Proteins ; Peptides ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2023-09-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1013745-2
ISSN	1460-2377 ; 0953-8178
ISSN (online)	1460-2377
ISSN	0953-8178
DOI	10.1093/intimm/dxad024
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Zs.A 2619: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Downregulation of HLA class II is associated with relapse after allogeneic stem cell transplantation and alters recognition by antigen-specific T cells.

Adachi, Yoshitaka / Sakai, Toshiyasu / Terakura, Seitaro / Shiina, Takashi / Suzuki, Shingo / Hamana, Hiroshi / Kishi, Hiroyuki / Sasazuki, Takehiko / Arase, Hisashi / Hanajiri, Ryo / Goto, Tatsunori / Nishida, Tetsuya / Murata, Makoto / Kiyoi, Hitoshi

International journal of hematology

2022 Volume 115, Issue 3, Page(s) 371–381

Abstract: Genomic deletion of donor-patient-mismatched HLA alleles in leukemic cells is a major cause of relapse after allogeneic hematopoietic stem cell transplantation (HSCT). Mismatched HLA is frequently lost as an individual allele or a whole region in HLA- ... ...

Abstract	Genomic deletion of donor-patient-mismatched HLA alleles in leukemic cells is a major cause of relapse after allogeneic hematopoietic stem cell transplantation (HSCT). Mismatched HLA is frequently lost as an individual allele or a whole region in HLA-class I, however, it is downregulated in HLA-class II. We hypothesized that there might be a difference in T cell recognition capacity against epitopes associated with HLA-class I and HLA-class II and consequently such allogeneic immune pressure induced HLA alterations in leukemic cells. To investigate this, we conducted in vitro experiments with T cell receptor-transduced T (TCR-T) cells. The cytotoxic activity of NY-ESO-1-specific TCR-T cells exhibited similarly against K562 cells with low HLA-A02:01 expression. However, we demonstrated that the cytokine production against low HLA-DPB105:01 expression line decreased gradually from the HLA expression level approximately 2-log lower than normal expressors. Using sort-purified leukemia cells before and after HSCT, we applied the next-generation sequencing, and revealed that there were several marked downregulations of HLA-class II alleles which demonstrated consistently low expression from pre-transplantation. The marked downregulation of HLA-class II may lead to decreased antigen recognition ability of antigen-specific T cells and may be one of immune evasion mechanism associated with HLA-class II downregulation.
MeSH term(s)	Alleles ; Down-Regulation ; Epitopes/immunology ; Graft vs Host Disease/genetics ; Graft vs Host Disease/immunology ; Graft vs Leukemia Effect/immunology ; Hematopoietic Stem Cell Transplantation ; Histocompatibility Antigens Class II/genetics ; Histocompatibility Antigens Class II/metabolism ; Humans ; K562 Cells ; Leukemia/genetics ; Leukemia/immunology ; Leukemia/therapy ; Recurrence ; T-Lymphocytes/immunology ; Transplantation, Homologous
Chemical Substances	Epitopes ; Histocompatibility Antigens Class II
Language	English
Publishing date	2022-01-17
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1076875-0
ISSN	1865-3774 ; 0917-1258 ; 0925-5710
ISSN (online)	1865-3774
ISSN	0917-1258 ; 0925-5710
DOI	10.1007/s12185-021-03273-w
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Book: MHC, pepuchido to shikkan

Sasazuki, Takehiko

(New medikaru saiensu ; 32)

1995

Title translation	MHC, peptides and diseases.
Author's details	Sasatsuki Yasuhiko hen
Series title	New medikaru saiensu ; 32
MeSH term(s)	Major Histocompatibility Complex/physiology ; Receptors, Antigen, T-Cell/physiology ; Peptides/immunology
Language	Japanese
Size	164 p. :, ill.
Edition	Shohan.
Publisher	Yōdosha
Publishing place	Tōkyō
Document type	Book
ISBN	9784897065311 ; 4897065313
Database	Catalogue of the US National Library of Medicine (NLM)

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Article: Introduction from the Co-Chairmen of the US and Japanese delegation of the US-Japan Cooperative Medical Science Program.

Haase, Ashley T / Sasazuki, Takehiko

Tuberculosis (Edinburgh, Scotland)

2007 Volume 87 Suppl 1, Page(s) S3–4

MeSH term(s)	Asia/epidemiology ; Communicable Diseases, Emerging/diagnosis ; Communicable Diseases, Emerging/epidemiology ; Congresses as Topic ; Humans ; United States
Language	English
Publishing date	2007-08
Publishing country	Scotland
Document type	Editorial
ZDB-ID	2046804-0
ISSN	1873-281X ; 1472-9792
ISSN (online)	1873-281X
ISSN	1472-9792
DOI	10.1016/j.tube.2007.05.004
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Article ; Online: Dual blockade of macropinocytosis and asparagine bioavailability shows synergistic anti-tumor effects on KRAS-mutant colorectal cancer.

Cancer letters

2021 Volume 522, Page(s) 129–141

Abstract: Mutations of KRAS gene are found in various types of cancer, including colorectal cancer (CRC). Despite intense efforts, no pharmacological approaches are expected to be effective against KRAS-mutant cancers. Macropinocytosis is an evolutionarily ... ...

Abstract	Mutations of KRAS gene are found in various types of cancer, including colorectal cancer (CRC). Despite intense efforts, no pharmacological approaches are expected to be effective against KRAS-mutant cancers. Macropinocytosis is an evolutionarily conserved actin-dependent endocytic process that internalizes extracellular fluids into large vesicles called macropinosomes. Recent studies have revealed macropinocytosis's important role in metabolic adaptation to nutrient stress in cancer cells harboring KRAS mutations. Here we showed that KRAS-mutant CRC cells enhanced macropinocytosis for tumor growth under nutrient-depleted conditions. We also demonstrated that activation of Rac1 and phosphoinositide 3-kinase were involved in macropinocytosis of KRAS-mutant CRC cells. Furthermore, we found that macropinocytosis was closely correlated with asparagine metabolism. In KRAS-mutant CRC cells engineered with knockdown of asparagine synthetase, macropinocytosis was accelerated under glutamine-depleted condition, and albumin addition could restore the glutamine depletion-induced growth suppression by recovering the intracellular asparagine level. Finally, we discovered that the combination of macropinocytosis inhibition and asparagine depletion dramatically suppressed the tumor growth of KRAS-mutant CRC cells in vivo. These results indicate that dual blockade of macropinocytosis and asparagine bioavailability could be a novel therapeutic strategy for KRAS-mutant cancers.
MeSH term(s)	Asparagine/genetics ; Asparagine/metabolism ; Aspartate-Ammonia Ligase/antagonists & inhibitors ; Aspartate-Ammonia Ligase/genetics ; Cell Line, Tumor ; Cell Proliferation/genetics ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/therapy ; Gene Knockdown Techniques ; Humans ; Mutation/genetics ; Phosphatidylinositol 3-Kinases/genetics ; Pinocytosis/genetics ; Proto-Oncogene Proteins p21(ras)/genetics ; rac1 GTP-Binding Protein/genetics
Chemical Substances	KRAS protein, human ; RAC1 protein, human ; Asparagine (7006-34-0) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; rac1 GTP-Binding Protein (EC 3.6.5.2) ; Aspartate-Ammonia Ligase (EC 6.3.1.1)
Language	English
Publishing date	2021-09-20
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	195674-7
ISSN	1872-7980 ; 0304-3835
ISSN (online)	1872-7980
ISSN	0304-3835
DOI	10.1016/j.canlet.2021.09.023
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Zs.A 1177: Show issues

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Article ; Online: Substantially increased risk of cancer in patients with diabetes mellitus: a systematic review and meta-analysis of epidemiologic evidence in Japan.

Noto, Hiroshi / Osame, Keiichiro / Sasazuki, Takehiko / Noda, Mitsuhiko

Journal of diabetes and its complications

2010 Volume 24, Issue 5, Page(s) 345–353

Abstract: Aims: Several meta-analyses have shown that diabetes mellitus affects the risk of certain site-specific cancers. However, a meta-analysis on the overall risk of cancer has not yet been performed.: Methods: We performed a search of MEDLINE and the ... ...

Abstract	Aims: Several meta-analyses have shown that diabetes mellitus affects the risk of certain site-specific cancers. However, a meta-analysis on the overall risk of cancer has not yet been performed. Methods: We performed a search of MEDLINE and the Cochrane Library for pertinent articles (including their references) that had been published as of June 10, 2010. English-language, original observational cohort studies and case-control studies conducted in Japan were included for a qualitative review and a meta-analysis. Results: A total of 22,485 cancer cases were reported in four cohort studies and one case-control study (with a total of 250,479 subjects). With these five reports, a meta-analysis of the all-cancer risk in both men and women showed an increased risk in subjects with diabetes, compared with nondiabetic subjects (OR 1.70, 95% CI 1.38-2.10). The increase in the risk ratio adjusted for possible confounders was significant in men and borderline in women (adjusted RR 1.25, 95% CI 1.06-1.46 in men; adjusted RR 1.23, 95% CI 0.97-1.56 in women). An analysis of site-specific cancers revealed increased risks for incident hepatocellular cancer (OR 3.64, 95% CI 2.61-5.07) and endometrial cancer (OR 3.43, 95% CI 1.53-7.72). Conclusions: As is the case in Western countries, Asian people with diabetes have a higher risk of incident cancer than those without diabetes. Cancer prevention and early detection should be important components of diabetes management in light of the exponentially increasing prevalence of diabetes, which has substantial implications in public health and clinical practices.
MeSH term(s)	Adult ; Aged ; Carcinoma, Hepatocellular/epidemiology ; Diabetes Mellitus/epidemiology ; Endometrial Neoplasms/epidemiology ; Female ; Humans ; Japan/epidemiology ; Liver Neoplasms/epidemiology ; Male ; Middle Aged ; Neoplasms/epidemiology ; Prevalence ; Risk
Language	English
Publishing date	2010-09
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1105840-7
ISSN	1873-460X ; 1056-8727
ISSN (online)	1873-460X
ISSN	1056-8727
DOI	10.1016/j.jdiacomp.2010.06.004
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