scholarly journals The ubiquitin-like modifier FAT10 – much more than a proteasome-targeting signal

2020 ◽  
Vol 133 (14) ◽  
pp. jcs246041
Author(s):  
Annette Aichem ◽  
Marcus Groettrup
Keyword(s):  
Current Knowledge ◽  
Human Leukocyte ◽  
Cell Types ◽  
26S Proteasome ◽  
Covalent Interaction ◽  
Leukocyte Antigen ◽  
Differential Outcomes ◽  
Interaction Partners ◽  
Targeting Signal ◽  
Necrosis Factor

ABSTRACTHuman leukocyte antigen (HLA)-F adjacent transcript 10 (FAT10) also called ubiquitin D (UBD) is a member of the ubiquitin-like modifier (ULM) family. The FAT10 gene is localized in the MHC class I locus and FAT10 protein expression is mainly restricted to cells and organs of the immune system. In all other cell types and tissues, FAT10 expression is highly inducible by the pro-inflammatory cytokines interferon (IFN)-γ and tumor necrosis factor (TNF). Besides ubiquitin, FAT10 is the only ULM which directly targets its substrates for degradation by the 26S proteasome. This poses the question as to why two ULMs sharing the proteasome-targeting function have evolved and how they differ from each other. This Review summarizes the current knowledge of the special structure of FAT10 and highlights its differences from ubiquitin. We discuss how these differences might result in differential outcomes concerning proteasomal degradation mechanisms and non-covalent target interactions. Moreover, recent insights about the structural and functional impact of FAT10 interacting with specific non-covalent interaction partners are reviewed.

Imaging to Differentiate the Various Forms of Seronegative Arthritis

2018 ◽  
Vol 22 (02) ◽  
pp. 189-196
Author(s):  
Kay-Geert Hermann ◽  
Anna Zejden ◽  
Iwona Sudoł-Szopińska ◽  
Iris Eshed
Keyword(s):  
Human Leukocyte ◽  
Leukocyte Antigen ◽  
Important Diagnostic Tool ◽  
Inflammatory Bowel ◽  
Diagnostic Work ◽  
Factor Α ◽  
Work Up ◽  
Necrosis Factor

AbstractSpondyloarthritis (SpA) is a group of diseases characterized by back pain, spinal inflammation, human leukocyte antigen-B27 positivity, and peripheral findings such as dactylitis, enthesitis, and uveitis. It includes ankylosing spondylitis, psoriatic arthritis, reactive arthritis, arthritis associated with inflammatory bowel disease, and undifferentiated SpA. The role of imaging in the diagnosis, management, and follow-up of patients with SpA has become dramatically more important with the introduction of new therapies such as tumor necrosis factor-α inhibitors. Although in many instances differentiating between the SpA entities is straightforward based on the clinical presentation, often such differentiation remains challenging, and categorization of an individual patient into a subset of SpA can be difficult. Imaging, mainly radiography and magnetic resonance imaging, serves as an important diagnostic tool. Diseases in the spondyloarthritis complex share common presentation but at the same time may have distinct radiographic phenotypes. We present these common and distinct imaging manifestations that may potentially help distinguish between the entities in the diagnostic work-up.

Association of tumor necrosis factor and human leukocyte antigen DRB1 alleles with Graves' ophthalmopathy

2004 ◽  
Vol 65 (6) ◽  
pp. 632-639 ◽  
Author(s):  
Tomasz Bednarczuk ◽  
Yuji Hiromatsu ◽  
Naoko Seki ◽  
Rafał Płoski ◽  
Tomoka Fukutani ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Human Leukocyte Antigen ◽  
Tumor Necrosis ◽  
Human Leukocyte ◽  
Leukocyte Antigen ◽  
Graves Ophthalmopathy ◽  
Necrosis Factor

Survival of Malnourished Head and Neck Cancer Patients Can Be Predicted by Human Leukocyte Antigen-DR Expression and Interleukin-6/Tumor Necrosis Factor-α Response of the Monocyte

2000 ◽  
Vol 24 (6) ◽  
pp. 329-336 ◽  
Author(s):  
Marian A. E. van Bokhorst-de van der Schueren ◽  
B. Mary E. von Blomberg-van der Flier ◽  
Dirk J. Kuik ◽  
Petra E. T. Scholten ◽  
Michiel P. C. Siroen ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Tumor Necrosis Factor ◽  
Cancer Patients ◽  
Interleukin 6 ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Human Leukocyte ◽  
Leukocyte Antigen ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Class I major histocompatibility complex-restricted cytotoxic T lymphocytes specific for Epstein-Barr virus (EBV)-transformed B lymphoblastoid cell lines against which they were raised.

1995 ◽  
Vol 181 (6) ◽  
pp. 2221-2228 ◽  
Author(s):  
A B Hill ◽  
S P Lee ◽  
J S Haurum ◽  
N Murray ◽  
Q Y Yao ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Cytotoxic T Lymphocytes ◽  
Tumor Necrosis ◽  
Epstein Barr Virus ◽  
Human Leukocyte ◽  
Leukocyte Antigen ◽  
Barr Virus ◽  
Epstein Barr ◽  
Necrosis Factor ◽  
Factor Release

We have raised CD8+ cytotoxic T lymphocytes (CTL) from three Epstein-Barr virus-seropositive donors by incubating peripheral blood lymphocytes with irradiated autologous B95.8-strain EBV-transformed B lymphoblastoid cells (LCL). However, to detect lysis in a standard 51Cr release assay of the LCL against which these CTL were raised, superinfection with recombinant vaccinia expressing the appropriate EBV protein or incubation with the peptide epitope was necessary. The untreated LCL were not lysed, even though Western blotting demonstrated that they expressed the EBV antigens containing the CTL epitopes. We have found CTL of this phenotype that are restricted by human leukocyte antigen-A2, -A3, -B7, or -B39, and which recognize the EBV latent proteins, EBV nuclear antigen (EBNA)-3A, EBNA-3C, or terminal protein. During these experiments, we identified a new human leukocyte antigen-A3-restricted EBNA-3A epitope, residues 603-611, RLRAEAGVK. We raised a spontaneous LCL, transformed by endogenous EBV, from one donor, but this was also not lysed. For at least one of the epitopes, CTL from another donor lysed the LCL without superinfection or addition of peptides. We conclude that the CTL were unable to achieve a high enough avidity of interaction with untreated LCL to trigger effector function, although the LCL were able to stimulate them to grow in vitro for up to 4 mo. To assess whether a small percentage of the LCL might possess a higher antigen density, we used an assay of tumor necrosis factor release from a CTL clone, which was able to detect antigen-bearing cells representing only 1% of a stimulating LCL population. Nevertheless, the untreated autologous LCL line failed to stimulate tumor necrosis factor release.

Abstract 292: Hypoxia Induced Formation of Immunoproteasome Instigates Rejection of Allogeneic Mesenchymal Stem Cells in the Ischemic Heart

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Ejlal Abu-El-Rub ◽  
Weiang Yan ◽  
Niketa Sareen ◽  
Keshav N Alagarsamy ◽  
Alireza Rafieerad ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Leukocyte ◽  
Cardiac Repair ◽  
26S Proteasome ◽  
Ischemic Heart ◽  
Host Immune System ◽  
Poor Survival ◽  
Allogeneic Mscs ◽  
Leukocyte Antigen

Bone marrow derived allogeneic (donor derived) mesenchymal stem cells (MSCs) are considered to be prominent cell type for cardiac repair following a damage due to ischemic heart disease. Even though the outcome of initial allogeneic MSCs based clinical trials was encouraging, the overall enthusiasm lately has declined due to poor survival of transplanted cells in the ischemic heart. We reported in a rat model of myocardial infarction that allogeneic-MSCs became immunogenic after 5 weeks of transplantation and were rejected by host immune system that led to poor survival of implanted cells. The immunoprivilege of MSCs is preserved by absence of cell surface antigen, human leukocyte antigen (HLA) - DRα. We found that in normoxic MSCs, 26S proteasome degrades HLA-DRα and maintains immunoprivilege of MSCs. The exposure to hypoxia leads to inactivation of 26S proteasome and formation of immunoproteasome in MSCs, which is associated with upregulation and activation of HLA-DRα, and as a result MSCs become immunogenic. Furthermore, inhibition of immunoproteasome formation in hypoxic MSCs preserves the immunoprivilege. Therefore, hypoxia induced shift in the phenotype of proteasome from 26S toward immunoproteasome triggers loss of immunoprivilege of allogeneic MSCs and rejection. In our ongoing studies we are investigating if preventing the formation of immunoproteasome would prevent rejection of allogeneic MSCs in the ischemic heart and improve survival of transplanted cells. The outcome of these studies may provide molecular targets to plan interventions to preserve immunoprivilege of allogeneic MSCs in the ischemic heart and improve benefits of allogeneic MSCs for cardiac repair.

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