Article
Biochemistry & Molecular Biology
Jieru Deng, Chunni Lu, Chuanxin Liu, Sara Oveissi, W. Douglas Fairlie, Erinna F. Lee, Pamuk Bilsel, Hamsa Puthalakath, Weisan Chen
Summary: The study demonstrates that IAV infection induces endogenous presentation of a viral epitope by MHC-II to CD4(+) T cells, dependent on de novo protein synthesis and the ER-Golgi network. Some antigenic peptides are of cytosolic origin in this process. Additionally, autophagy inhibitors and deletion of autophagy-related genes block most of the MHC-II-restricted endogenous IAV antigen presentation.
Article
Immunology
Fabrizio Celesti, Andrea Gatta, Mariam Shallak, Anna Maria Chiaravalli, Michele Cerati, Fausto Sessa, Roberto S. Accolla, Greta Forlani
Summary: In an animal experimental system, vaccination with glioblastoma GL261 cells expressing CIITA showed successful protection against glioblastoma growth. The activation of MHC class II through CIITA led to rapid infiltration of CD4+ and CD8+ T cells, resulting in the rejection or retardation of tumor growth. This approach demonstrates the potential application of novel immunotherapeutic strategies in the clinical setting.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Physics, Multidisciplinary
Matan Even Tzur, Ofer Neufeld, Avner Fleischer, Oren Cohen
Summary: Floquet systems often exhibit dynamical symmetries (DS) that govern the time-dependent dynamics and result in selection rules. When these symmetries are broken, deviations in selection rules are systematically imposed on the symmetry-broken system, which manifest as scaling laws of these deviations. This discovery provides a new insight into the interplay between selection rule deviations, symmetry breaking perturbations, and broken dynamical symmetries.
NEW JOURNAL OF PHYSICS
(2021)
Article
Evolutionary Biology
Xiaolin Li, Tong Liu, Aoqiang Li, Yanhong Xiao, Keping Sun, Jiang Feng
Summary: This study investigated the mechanisms influencing the diversity and genetic differentiation of MHC genes in the greater horseshoe bat. The results showed that environmental stress and selective pressure influence MHC diversity, and climate factors play a role in local adaptation.
EVOLUTIONARY APPLICATIONS
(2023)
Article
Immunology
Nadezhda Logunova, Marina Kapina, Elena Kondratieva, Alexander Apt
Summary: By analyzing the role of MHC-II genes in the control of tuberculosis infection, it was found that the H2-Ab gene plays a major role. Further research revealed that regular genetic recombination within the MHC-II recombination hot spot region can severely impair immune system functioning.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Bo Zhao, Lijun Sun, Qing Yuan, Zhenzhen Hao, Fei An, Wanting Zhang, Xiaoshuang Zhu, Bing Wang
Summary: The absence of BAP31 leads to an enlarged spleen and thymus in mice, accompanied by activated clustering and disrupted differentiation of CD4(+)T cells. In vitro co-culture studies show that the loss of BAP31 increases the expression of antigen presenting molecules, particularly MHC-II, on macrophages. These findings suggest that BAP31 regulates the activation and differentiation of CD4+T cells by modulating MHC class II molecule expression on macrophages.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Physical
Thom H. Dunning Jr, Lu T. Xu
Summary: This study extends the investigation of the effect of dynamical electron correlation on covalent and recoupled pair bonds in the excited states of CH and CF molecules. It reveals that dynamical correlation is less important in the a(4)sigma(-) states and causes smaller changes in bond energies compared to the X-2 pi states. However, changes in bond distance and vibrational frequency are affected by the changes in the slope and curvature of the dynamical electron correlation energy.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Immunology
Yun Zhao, Juan Xiong, Hai-Xia Chen, Min Zhang, Li-Na Zhou, Yin-Fang Wu, Wei-Jie Li, Xia Fei, Fei Li, Chen Zhu, Wen Li, Song-Min Ying, Lie Wang, Zhi-Hua Chen, Hua-Hao Shen
Summary: This study identified a new spontaneous mutation causing MHC II deficiency in mice and provided a new paradigm for explaining type II BLS in mice.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Genetics & Heredity
Kazuyoshi Ishigaki, Kaitlyn Lagattuta, Yang Luo, Eddie James, Jane Buckner, Soumya Raychaudhuri
Summary: Genetic analyses provide evidence supporting the central hypothesis that HLA alleles influence T cell receptor composition and increase the risk of autoimmune diseases.
Review
Immunology
Cornelia Heuberger, Johanna Pott, Kevin Joseph Maloy
Summary: Intestinal epithelial cells play a dual role in antigen presentation, potentially activating effector T cells while also suppressing immune responses through regulatory T cell activation. The expression of MHC class II on IECs is tightly regulated and its impact on immune responses can vary depending on the specific conditions and cellular context.
Article
Immunology
Lili Tang, Ge Li, Yang Zheng, Chunmei Hou, Yang Gao, Ying Hao, Zhenfang Gao, Rongliang Mo, Yuxiang Li, Beifen Shen, Renxi Wang, Zhiding Wang, Gencheng Han
Summary: In this study, it was discovered that Tim-3 induces immune tolerance by suppressing MHC-II expression in macrophages, inhibiting MHC-II-mediated autoantigen presentation and CD4(+)T cell activation. This finding provides a new solution for multiple sclerosis treatment.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Longdan Kang, Si Wang, Dalu Wang, Jia Wang, Rui Zheng, Xiaofeng Jiang, Beixing Liu
Summary: During respiratory syncytial virus (RSV) infection, pulmonary ILC2 cells may function as antigen-presenting cells to induce the activation of CD4+ T cells through the MHC II pathway.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Oncology
Simone Stupia, Christina Heeke, Alicia Bruggemann, Anne Zaremba, Beatrice Thier, Julia Kretz, Antje Sucker, Manuel Philip, Gennadiy Zelinskyy, Soldano Ferrone, Alexander Roesch, Susanne Horn, Eva Hadaschik, Dirk Schadendorf, Mirko Trilling, Ulf Dittmer, Klaus Griewank, Fang Zhao, Annette Paschen
Summary: Recent studies have shown that cytotoxic CD4 T cells can kill melanoma cells dependent on HLA class II (HLA-II). This study investigates the evolution of HLA-II-loss tumors that evade cytotoxic CD4 T cell activity and contribute to immunotherapy resistance. The findings highlight the importance of tumor cell-intrinsic HLA-II antigen presentation in disease control and suggest the need to overcome its down-regulation for better patient outcomes.
CLINICAL CANCER RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Carley Tasker, Jenny Patel, Vibha Jawa, Jad Maamary
Summary: A novel cell-based assay has been proposed for investigating the endosomal processing and MHC class II presentation capabilities of antigens, utilizing competition between epitopes for MHC class II binding and labeled soluble T cell receptors as detectors for epitope presentation.
Article
Immunology
Patricia T. Illing, Andy van Hateren, Rachel Darley, Nathan P. Croft, Nicole A. Mifsud, Samuel King, Lyudmila Kostenko, Mandvi Bharadwaj, James McCluskey, Tim Elliott, Anthony W. Purcell
Summary: Abacavir hypersensitivity syndrome occurs in individuals with a specific gene expression, altering immune responses. Research shows that abacavir affects the assembly of HLA-B*57:01 complexes.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Jaime Agudo-Canalejo, Sebastian W. Schultz, Haruka Chino, Simona M. Migliano, Chieko Saito, Ikuko Koyama-Honda, Harald Stenmark, Andreas Brech, Alexander I. May, Noboru Mizushima, Roland L. Knorr
Summary: This study explores how autophagosomes sequester droplets containing p62 protein in cells and demonstrates the formation of double-membrane, autophagosome-like vesicles on protein-free droplets through partial wetting in vitro. A minimal physical model shows that droplet surface tension supports the formation of membrane sheets. The interaction between the material properties of droplets and membrane sheets elucidates the mechanisms underlying droplet autophagy.
Editorial Material
Cell Biology
Hideaki Morishita, Yuki Kanda, Noboru Mizushima
Summary: Macroautophagy plays a crucial role in the maturation of lamellar bodies, by fusing with immature lamellar bodies to increase their size and lipid contents. This function is essential for respiration after birth in mice and for maintaining buoyancy in zebrafish.
Editorial Material
Cell Biology
Sebastian W. Schultz, Jaime Agudo-Canalejo, Haruka Chino, Simona M. Migliano, Chieko Saito, Ikuko Koyama-Honda, Harald Stenmark, Andreas Brech, Noboru Mizushima, Roland L. Knorr, Alexander I. May
Summary: The wetting interactions between autophagic membranes and phase-separated droplets play a crucial role in determining the structure and fate of forming autophagosomes.
Editorial Material
Cell Biology
Willa Wen-You Yim, Noboru Mizushima
Summary: The study reveals that the SARS-CoV-2 protein ORF3a disrupts autophagy by interfering with the fusion between autophagosomes and lysosomes, through dysregulation of the HOPS complex.
DEVELOPMENTAL CELL
(2021)
Article
Biochemistry & Molecular Biology
Kaito Mimura, Jun-Ichi Sakamaki, Hideaki Morishita, Masahito Kawazu, Hiroyuki Mano, Noboru Mizushima
Summary: Autophagy is a process that degrades cytoplasmic material in lysosomes and undergoes dynamic regulation in response to cellular stress. A genome-wide CRISPR screen identified a component of the de novo purine synthesis pathway as a negative regulator of autophagy. These findings suggest a potential role for nucleotide metabolism in autophagy regulation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Cell Biology
Fumiya Okawa, Yutaro Hama, Sidi Zhang, Hideaki Morishita, Hayashi Yamamoto, Tim P. Levine, Noboru Mizushima
Summary: TMEM41B and VMP1 are ER-localizing proteins crucial for cellular processes such as autophagosome formation and lipid droplet homeostasis. A new superfamily named DedA superfamily, consisting of TMEM41, VMP1, DedA and PF06695 families, was identified. Structural prediction and biochemical verification suggest a potential ion-coupled transport function for DedA superfamily proteins.
JOURNAL OF CELL SCIENCE
(2021)
Article
Multidisciplinary Sciences
Hideaki Morishita, Tomoya Eguchi, Satoshi Tsukamoto, Yuriko Sakamaki, Satoru Takahashi, Chieko Saito, Ikuko Koyama-Honda, Noboru Mizushima
Summary: The study reveals the essential role of phospholipases in the PLAAT family in the degradation of lens organelles, with Plaat1 in zebrafish and PLAAT3 in mice translocating to organelles before inducing their rupture and degradation. This process is mediated by Hsf4 and is crucial for maintaining the transparency and refractive function of the lens in vertebrates.
Editorial Material
Cell Biology
Hideaki Morishita, Tomoya Eguchi, Noboru Mizushima
Summary: The PLAAT-family phospholipases degrade organelles in lens fiber cells independently of macroautophagy during terminal differentiation, shedding light on a new mechanism of intracellular degradation with significant physiological relevance.
News Item
Biochemistry & Molecular Biology
Yutaro Hama, Sidi Zhang, Noboru Mizushima
Summary: This study explores how Nbr1 in fission yeast recognizes vacuolar hydrolases Ams1 and Ape4 through versatile and cargo-specific interactions with the Nbr1 ZZ1 domain.
Article
Cell Biology
Willa Wen-You Yim, Yoshitaka Kurikawa, Noboru Mizushima
Summary: Since the 1950s, the field of autophagy research has experienced exponential growth in publications, providing a wealth of information for researchers but also posing challenges for newcomers. The publication trend in the autophagy field can be separated into three phases, with the recent rapid increase likely driven by highly cited research papers from previous phases, leading to a wider variety of research topics, especially those related to diseases and modulating autophagy.
Review
Biochemistry & Molecular Biology
Yutaro Hama, Hideaki Morishita, Noboru Mizushima
Summary: The endoplasmic reticulum is essential for the biogenesis of various organelles and lipid-containing structures. Recent studies have shown that VMP1 and TMEM41B, two ER membrane proteins, play important roles in the formation of ER-derived structures and lipid scrambling activity.
Article
Cell Biology
Sidi Zhang, Euki Yazaki, Hirokazu Sakamoto, Hayashi Yamamoto, Noboru Mizushima
Summary: The ATG ubiquitin-like conjugation systems, ATG12 and ATG8, play important roles in macroautophagy. This study constructs a transcriptome database and identifies ATG conjugation system components in 94 eukaryotic species. It finds that functional diversification of these systems is more common than previously thought.
Editorial Material
Cell Biology
Ikuko Koyama-Honda, Noboru Mizushima
Summary: This article summarizes the current understanding of the mechanism of STX17 translocation and the duration of its stay during the fusion process between autophagosomes and lysosomes, and discusses unresolved questions.
Article
Biochemistry & Molecular Biology
Haruka Chino, Akinori Yamasaki, Koji L. Ode, Hiroki R. Ueda, Nobuo N. Noda, Noboru Mizushima
Summary: This study reveals the critical role of LIR phosphorylation in the interaction, localization, and initiation of autophagy of the ER-phagy receptor TEX264 with ATG8. Structural analysis shows that phosphorylation increases binding affinity by generating multiple hydrogen bonds with ATG8, which cannot be mimicked by acidic residues. This finding highlights the importance of LIR phosphorylation in LIR-ATG8 interactions.
Article
Biochemistry & Molecular Biology
Willa Wen-You Yim, Hayashi Yamamoto, Noboru Mizushima
Summary: Damaged lysosomes can be repaired by the calcium release-dependent recruitment of the ESCRT machinery. However, the involvement of annexins in this process has not been fully understood. This study shows that ANXA1 and ANXA2 are important for the repair of damaged lysosomes, and their recruitment is calcium-dependent and independent of the ESCRT mechanism.