Cutting an NKG2D Ligand Short: Cellular Processing of the Peculiar Human NKG2D Ligand ULBP4
Stress-induced cell surface expression of MHC class I-related glycoproteins of the MIC and ULBP families allows for immune recognition of dangerous “self cells” by human cytotoxic lymphocytes via the NKG2D receptor. With two MIC molecules (MICA and MICB) and six ULBP molecules (ULBP1–6), there are a...
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2018-03-01
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doaj-61e53d9d15c547bea43272d0c62b53572020-11-24T23:44:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-03-01910.3389/fimmu.2018.00620354024Cutting an NKG2D Ligand Short: Cellular Processing of the Peculiar Human NKG2D Ligand ULBP4Tobias Zöller0Mareike Wittenbrink1Meike Hoffmeister2Meike Hoffmeister3Alexander Steinle4Institute for Molecular Medicine, Goethe University Frankfurt am Main, Frankfurt am Main, GermanyInstitute for Molecular Medicine, Goethe University Frankfurt am Main, Frankfurt am Main, GermanyInstitute of Biochemistry II, Goethe University Frankfurt am Main, Frankfurt am Main, GermanyBrandenburg Medical School (MHB) Theodor Fontane, Institute of Biochemistry, Neuruppin, GermanyInstitute for Molecular Medicine, Goethe University Frankfurt am Main, Frankfurt am Main, GermanyStress-induced cell surface expression of MHC class I-related glycoproteins of the MIC and ULBP families allows for immune recognition of dangerous “self cells” by human cytotoxic lymphocytes via the NKG2D receptor. With two MIC molecules (MICA and MICB) and six ULBP molecules (ULBP1–6), there are a total of eight human NKG2D ligands (NKG2DL). Since the discovery of the NKG2D–NKG2DL system, the cause for both redundancy and diversity of NKG2DL has been a major and ongoing matter of debate. NKG2DL diversity has been attributed, among others, to the selective pressure by viral immunoevasins, to diverse regulation of expression, to differential tissue expression as well as to variations in receptor interactions. Here, we critically review the current state of knowledge on the poorly studied human NKG2DL ULBP4. Summarizing available facts and previous studies, we picture ULBP4 as a peculiar ULBP family member distinct from other ULBP family members by various aspects. In addition, we provide novel experimental evidence suggesting that cellular processing gives rise to mature ULBP4 glycoproteins different to previous reports. Finally, we report on the proteolytic release of soluble ULBP4 and discuss these results in the light of known mechanisms for generation of soluble NKG2DL.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00620/fullNKG2DULBP4NK cellssheddingantibodies |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tobias Zöller Mareike Wittenbrink Meike Hoffmeister Meike Hoffmeister Alexander Steinle |
spellingShingle |
Tobias Zöller Mareike Wittenbrink Meike Hoffmeister Meike Hoffmeister Alexander Steinle Cutting an NKG2D Ligand Short: Cellular Processing of the Peculiar Human NKG2D Ligand ULBP4 Frontiers in Immunology NKG2D ULBP4 NK cells shedding antibodies |
author_facet |
Tobias Zöller Mareike Wittenbrink Meike Hoffmeister Meike Hoffmeister Alexander Steinle |
author_sort |
Tobias Zöller |
title |
Cutting an NKG2D Ligand Short: Cellular Processing of the Peculiar Human NKG2D Ligand ULBP4 |
title_short |
Cutting an NKG2D Ligand Short: Cellular Processing of the Peculiar Human NKG2D Ligand ULBP4 |
title_full |
Cutting an NKG2D Ligand Short: Cellular Processing of the Peculiar Human NKG2D Ligand ULBP4 |
title_fullStr |
Cutting an NKG2D Ligand Short: Cellular Processing of the Peculiar Human NKG2D Ligand ULBP4 |
title_full_unstemmed |
Cutting an NKG2D Ligand Short: Cellular Processing of the Peculiar Human NKG2D Ligand ULBP4 |
title_sort |
cutting an nkg2d ligand short: cellular processing of the peculiar human nkg2d ligand ulbp4 |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2018-03-01 |
description |
Stress-induced cell surface expression of MHC class I-related glycoproteins of the MIC and ULBP families allows for immune recognition of dangerous “self cells” by human cytotoxic lymphocytes via the NKG2D receptor. With two MIC molecules (MICA and MICB) and six ULBP molecules (ULBP1–6), there are a total of eight human NKG2D ligands (NKG2DL). Since the discovery of the NKG2D–NKG2DL system, the cause for both redundancy and diversity of NKG2DL has been a major and ongoing matter of debate. NKG2DL diversity has been attributed, among others, to the selective pressure by viral immunoevasins, to diverse regulation of expression, to differential tissue expression as well as to variations in receptor interactions. Here, we critically review the current state of knowledge on the poorly studied human NKG2DL ULBP4. Summarizing available facts and previous studies, we picture ULBP4 as a peculiar ULBP family member distinct from other ULBP family members by various aspects. In addition, we provide novel experimental evidence suggesting that cellular processing gives rise to mature ULBP4 glycoproteins different to previous reports. Finally, we report on the proteolytic release of soluble ULBP4 and discuss these results in the light of known mechanisms for generation of soluble NKG2DL. |
topic |
NKG2D ULBP4 NK cells shedding antibodies |
url |
http://journal.frontiersin.org/article/10.3389/fimmu.2018.00620/full |
work_keys_str_mv |
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