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Live-cell single-molecule imaging of the cytokine receptor MPL for analysis of dynamic dimerization

Journal of Molecular Cell Biology 2016年第6期8卷 553-555页

作者： Akihiko Sakamoto Takashi Tsukamoto Yuji Furutani Yuki Sudo Kazuyuki Shimada Akihiro Tomita hitos.i kiyoi Takashi Kato Takashi Funatsu Graduate School of Pharmaceutical Sciences The University of TokyoTokyo 1130033Japan Department of Haematology and Oncology Nagoya University Graduate School of MedicineNagoya 4668550Japan Graduate School of Medicine Dentistry and Pharmaceutical SciencesOkayama UniversityOkayama 7008530Japan Department of Life and Coordination-Complex Molecular Science Institute for Molecular ScienceOkazaki 4448585Japan Department of Structural Molecular Science SOKENDAIOkazaki 4448585Japan Core Research for Evolutional Science and Technology Japan Science and Technology AgencyTokyo 1020076Japan institute for Advanced Research Nagoya UniversityNagoya 4648601Japan Department of Haematology Fujita Health University School of MedicineToyoake 4701192Japan Faculty of Education and integrated Arts and Sciences Waseda UniversityTokyo 1628480Japan

Dear Editor,MPL is a cytokine receptor that regulates the production of myeloid cells,in particular megakaryocytes and platelets(Kaushansky,2005).Dimerization of MPL is important not only for the initiation of signalling(Kaushansky,2005)but also for the resistance to a recent therapy for myeloproliferative neoplasms(Koppikar et al.,2012).in the current model,cytokine receptors exist as a mixture of monomers and dimers without ligand stimulation,while ligand binding induces additional receptor dimerization(Kaushansky,2005).

关键词： dimer dynamic analysis

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BCR–ABL-specific CD4^(+) T-helper cells promote the priming of antigen-specific cytotoxic T cells via dendritic cells

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Cellular & Molecular immunology 2018年第1期15卷 15-26页

作者： Norihiro Ueda Rong Zhang Minako Tatsumi Tian-YiLiu Shuichi Kitayama YutakaYasui Shiori Sugai Tatsuaki iwama Satoru Senju Seiji Okada Tetsuya Nakatsura Kiyotaka Kuzushima hitos.i kiyoi Tomoki Naoe Shin Kaneko Yasushi Uemura Division of immunology Aichi Cancer Center Research InstituteNagoya464-0021Japan Shin Kaneko Laboratory Department of Cell Growth and DifferentiationCenter for iPS cell Research and Application(CiRA)Kyoto UniversityKyoto606-8507Japan Department of Hematology and Oncology Nagoya University Graduate School of MedicineNagoya466-0065Japan Division of Cancer immunotherapy Exploratory Oncology Research&Clinical Trial CenterNational Cancer CenterKashiwa277-8577ChibaJapan Key Laboratory of Cancer Center Chinese PLA General HospitalBeijing100853China Department of immunogenetics Graduate School of Medical SciencesKumamoto UniversityKumamoto860-8556Japan Division of Hematopoiesis Center for AIDS ResearchKumamoto UniversityKumamoto860-0811Japan National Hospital Organization Nagoya Medical Center Nagoya460-0001Japan

The advent of tyrosine kinase inhibitor(TKi)therapy markedly improved the outcome of patients with chronic-phase chronic myeloid leukemia(CML).However,the poor prognosis of patients with advanced-phase CML and the lifelong dependency on TKis are remaining challenges;therefore,an effective therapeutic has been *** BCR–ABL p210 fusion protein’s junction region represents a leukemia-specific neoantigen and is thus an attractive target for antigen-specific T-cell ***–ABL p210 fusion-region-specific CD4+T-helper(Th)cells possess antileukemic potential,but their function remains *** this study,we established a BCR–ABL p210 b3a2 fusion-region-specific CD4+Th-cell clone(b3a2-specific Th clone)and examined its dendritic cell(DC)-mediated antileukemic *** b3a2-specific Th clone recognized the b3a2 peptide in the context of HLA-DRB1*09:01 and exhibited a Th1 *** of this clone through T-cell antigen receptor stimulation triggered DC maturation,as indicated by upregulated production of CD86 and iL-12p70 by DCs,which depended on CD40 ligation by CD40L expressed on b3a2-specific Th ***,in the presence of HLA-A*24:02-restricted Wilms tumor 1(WT1)235–243 peptide,DCs conditioned by b3a2-specific Th cells efficiently stimulated the primary expansion of WTi-specific cytotoxic T lymphocytes(CTLs).The expanded CTLs were cytotoxic toward WT1235–243-peptide-loaded HLA-A*24:02-positive cell lines and exerted a potent antileukemic effect in ***,the b3a2-specific Th-clone-mediated antileukemic CTL responses were strongly inhibited by both TKis and interferon-α.Our findings indicate a crucial role of b3a2-specific Th cells in leukemia antigen-specific CTL-mediated immunity and provide an experimental basis for establishing novel CML immunotherapies.

关键词： BCR-ABL cancer immunotherapy CML dendritic cell T helper cell

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