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Article ; Online: A novel, nonanaphylactogenic, bispecific IgE-CD3 antibody eliminates IgE(+) B cells.

Kirak, Oktay / Riethmüller, Gert

The Journal of allergy and clinical immunology

2015 Volume 136, Issue 3, Page(s) 800–802.e3

MeSH term(s)	Antibodies, Bispecific/pharmacology ; B-Lymphocytes/drug effects ; B-Lymphocytes/immunology ; B-Lymphocytes/pathology ; CD3 Complex/genetics ; CD3 Complex/immunology ; Coculture Techniques ; Gene Expression ; Humans ; Immunoglobulin E/genetics ; Immunoglobulin E/immunology ; Lymphocyte Activation/drug effects ; Lymphocyte Depletion/methods ; Protein Binding ; T-Lymphocytes, Cytotoxic/cytology ; T-Lymphocytes, Cytotoxic/drug effects ; T-Lymphocytes, Cytotoxic/immunology
Chemical Substances	Antibodies, Bispecific ; CD3 Complex ; Immunoglobulin E (37341-29-0)
Language	English
Publishing date	2015-09
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	121011-7
ISSN	1097-6825 ; 1085-8725 ; 0091-6749
ISSN (online)	1097-6825 ; 1085-8725
ISSN	0091-6749
DOI	10.1016/j.jaci.2015.02.017
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Book ; Online ; Thesis: Eliminierung IgE-positiver B-Lymphozyten mit Hilfe eines rekombinanten bispezifischen Anti-IgE-, Anti-CD3-Antikörpers

Kirak, Oktay [Verfasser]

2010

Author's details	vorgelegt von Oktay Kirak
Keywords	Medizin, Gesundheit ; Medicine, Health
Subject code	sg610
Language	German
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article ; Online: TRF2-mediated telomere protection is dispensable in pluripotent stem cells.

Markiewicz-Potoczny, Marta / Lobanova, Anastasia / Loeb, Anisha M / Kirak, Oktay / Olbrich, Teresa / Ruiz, Sergio / Lazzerini Denchi, Eros

Nature

2020 Volume 589, Issue 7840, Page(s) 110–115

Abstract: In mammals, telomere protection is mediated by the essential protein TRF2, which binds chromosome ends and ensures genome ... ...

Abstract	In mammals, telomere protection is mediated by the essential protein TRF2, which binds chromosome ends and ensures genome integrity
MeSH term(s)	Animals ; Cell Proliferation ; Cell Survival ; DNA Damage ; DNA-Binding Proteins/metabolism ; Female ; Gene Expression Regulation, Developmental ; Mice ; Mouse Embryonic Stem Cells/cytology ; Mouse Embryonic Stem Cells/metabolism ; Pluripotent Stem Cells/cytology ; Pluripotent Stem Cells/metabolism ; Telomere/metabolism ; Telomeric Repeat Binding Protein 2/deficiency ; Telomeric Repeat Binding Protein 2/genetics ; Telomeric Repeat Binding Protein 2/metabolism ; Totipotent Stem Cells/cytology ; Totipotent Stem Cells/metabolism ; Transcription Factors/metabolism ; Transcription, Genetic ; Tumor Suppressor p53-Binding Protein 1/metabolism
Chemical Substances	Brd2 protein, mouse ; DNA-Binding Proteins ; POT1b protein, mouse ; TRF2 protein, mouse ; Telomeric Repeat Binding Protein 2 ; Transcription Factors ; Trp53bp1 protein, mouse ; Tumor Suppressor p53-Binding Protein 1 ; Zscan4c protein, mouse
Language	English
Publishing date	2020-11-25
Publishing country	England
Document type	Journal Article
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-020-2959-4
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Zs.A 26: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Premature Activation of Immune Transcription Programs in Autoimmune-Predisposed Mouse Embryonic Stem Cells and Blastocysts.

Kirak, Oktay / Ke, Eugene / Yang, Kevin Y / Schwarz, Anna / Plate, Lars / Nham, Amy / Abadejos, Justin R / Valencia, Anna / Wiseman, R Luke / Lui, Kathy O / Ku, Manching

International journal of molecular sciences

2020 Volume 21, Issue 16

Abstract: Autoimmune diabetes is a complex multifactorial disease with genetic and environmental factors playing pivotal roles. While many genes associated with the risk of diabetes have been identified to date, the mechanisms by which external triggers contribute ...

Abstract	Autoimmune diabetes is a complex multifactorial disease with genetic and environmental factors playing pivotal roles. While many genes associated with the risk of diabetes have been identified to date, the mechanisms by which external triggers contribute to the genetic predisposition remain unclear. Here, we derived embryonic stem (ES) cell lines from diabetes-prone non-obese diabetic (NOD) and healthy C57BL/6 (B6) mice. While overall pluripotency markers were indistinguishable between newly derived NOD and B6 ES cells, we discovered several differentially expressed genes that normally are not expressed in ES cells. Several genes that reside in previously identified insulin-dependent diabetics (Idd) genomic regions were up-regulated in NOD ES cells. Gene set enrichment analysis showed that different groups of genes associated with immune functions are differentially expressed in NOD. Transcriptomic analysis of NOD blastocysts validated several differentially overexpressed Idd genes compared to B6. Genome-wide mapping of active histone modifications using ChIP-Seq supports active expression as the promoters and enhancers of activated genes are also marked by active histone modifications. We have also found that NOD ES cells secrete more inflammatory cytokines. Our data suggest that the known genetic predisposition of NOD to autoimmune diabetes leads to epigenetic instability of several Idd regions.
MeSH term(s)	Animals ; Autoimmunity/genetics ; Blastocyst/metabolism ; Chemokines/metabolism ; Chromatin/metabolism ; Diabetes Mellitus, Experimental/genetics ; Epigenesis, Genetic ; Immune System/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mouse Embryonic Stem Cells/metabolism ; Proteome/metabolism ; Proteomics ; Transcription, Genetic ; Transcriptome/genetics
Chemical Substances	Chemokines ; Chromatin ; Proteome
Language	English
Publishing date	2020-08-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21165743
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Article ; Online: Prediabetes Induced by a Single Autoimmune B Cell Clone.

Phillips, Nathaniel / Ke, Eugene / Nham, Amy / Seidl, Maximilian / Freeman, Brent / Abadejos, Justin R / Xiao, Changchun / Nemazee, David / Ku, Manching / Kirak, Oktay

Frontiers in immunology

2020 Volume 11, Page(s) 1073

Abstract: While B cells play a significant role in the onset of type-1 diabetes (T1D), little is know about their role in those early stages. Thus, to gain new insights into the role of B cells in T1D, we converted a physiological early pancreas-infiltrating B ... ...

Abstract	While B cells play a significant role in the onset of type-1 diabetes (T1D), little is know about their role in those early stages. Thus, to gain new insights into the role of B cells in T1D, we converted a physiological early pancreas-infiltrating B cell into a novel BCR mouse model using Somatic Cell Nuclear Transfer (SCNT). Strikingly, SCNT-derived B1411 model displayed neither developmental block nor anergy. Instead, B1411 underwent spontaneous germinal center reactions. Without T cell help, B1411-Rag1
MeSH term(s)	Animals ; Autoimmunity ; B-Lymphocytes/immunology ; Basidiomycota/genetics ; Basidiomycota/metabolism ; Calcium Signaling/immunology ; Chromatin Assembly and Disassembly ; Clone Cells/immunology ; Diabetes Mellitus, Experimental/etiology ; Diabetes Mellitus, Experimental/genetics ; Diabetes Mellitus, Experimental/immunology ; Female ; Gene Expression Profiling ; Glucose Tolerance Test ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Mice, Inbred NOD ; Mice, Knockout ; Models, Immunological ; Nuclear Transfer Techniques ; Prediabetic State/etiology ; Prediabetic State/genetics ; Prediabetic State/immunology ; Receptors, Antigen, B-Cell/genetics ; Receptors, Antigen, B-Cell/immunology
Chemical Substances	Receptors, Antigen, B-Cell
Language	English
Publishing date	2020-06-18
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.01073
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Article ; Online: Deconstructive somatic cell nuclear transfer reveals novel regulatory T-cell subsets.

Ku, Manching / Ke, Eugene / Sabouri-Ghomi, Mohsen / Abadejos, Justin R / Freeman, Brent / Nham, Amy / Phillips, Nathaniel / Yang, Kevin Y / Lui, Kathy O / Kirak, Oktay

The Journal of allergy and clinical immunology

2018 Volume 142, Issue 3, Page(s) 997–1000.e4

MeSH term(s)	Animals ; Cell Differentiation ; Female ; Homeodomain Proteins/genetics ; Mice, Inbred NOD ; Mice, Transgenic ; Nuclear Transfer Techniques ; Sequence Analysis, RNA ; T-Lymphocytes, Regulatory/cytology
Chemical Substances	Homeodomain Proteins ; RAG-1 protein (128559-51-3)
Language	English
Publishing date	2018-05-30
Publishing country	United States
Document type	Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	121011-7
ISSN	1097-6825 ; 1085-8725 ; 0091-6749
ISSN (online)	1097-6825 ; 1085-8725
ISSN	0091-6749
DOI	10.1016/j.jaci.2018.04.038
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Article ; Online: A catalytically inactive mutant of the deubiquitylase YOD-1 enhances antigen cross-presentation.

Sehrawat, Sharvan / Koenig, Paul-Albert / Kirak, Oktay / Schlieker, Christian / Fankhauser, Manuel / Ploegh, Hidde L

Blood

2012 Volume 121, Issue 7, Page(s) 1145–1156

Abstract: Antigen presenting cells (APCs) that express a catalytically inactive version of the deubiquitylase YOD1 (YOD1-C160S) present exogenous antigens more efficiently to CD8(+) T cells, both in vitro and in vivo. Compared with controls, immunization of YOD1- ... ...

Abstract	Antigen presenting cells (APCs) that express a catalytically inactive version of the deubiquitylase YOD1 (YOD1-C160S) present exogenous antigens more efficiently to CD8(+) T cells, both in vitro and in vivo. Compared with controls, immunization of YOD1-C160S mice led to greater expansion of specific CD8(+) T cells and showed improved control of infection with a recombinant -herpes virus, MHV-68, engineered to express SIINFEKL peptide, the ligand for the ovalbumin-specific TCR transgenic OT-I cells. Enhanced expansion of specific CD8(+) T cells was likewise observed on infection of YOD1-C160S mice with a recombinant influenza A virus expressing SIINFEKL. YOD1-C160S APCs retained antigen longer than did control APCs. Enhanced crosspresentation by YOD1-C160S APCs was transporter associated with antigen processing (TAP1)-independent but sensitive to inclusion of inhibitors of acidification and of the proteasome. The activity of deubiquitylating enzymes may thus help control antigenspecific CD8(+) T-cell responses during immunization.
MeSH term(s)	ATP Binding Cassette Transporter, Subfamily B, Member 2 ; ATP-Binding Cassette Transporters/deficiency ; ATP-Binding Cassette Transporters/genetics ; ATP-Binding Cassette Transporters/immunology ; Adoptive Transfer ; Animals ; Antigen-Presenting Cells/enzymology ; Antigen-Presenting Cells/immunology ; Brefeldin A/pharmacology ; CD8-Positive T-Lymphocytes/immunology ; Cross-Priming/drug effects ; Cross-Priming/genetics ; Female ; Hydrogen-Ion Concentration ; Immunization ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Mutation, Missense ; Ovalbumin/immunology ; Peptide Fragments/immunology ; Rhadinovirus/immunology ; Rhadinovirus/pathogenicity ; Ubiquitin Thiolesterase/genetics ; Ubiquitin Thiolesterase/immunology ; Ubiquitin Thiolesterase/metabolism
Chemical Substances	ATP Binding Cassette Transporter, Subfamily B, Member 2 ; ATP-Binding Cassette Transporters ; OVA-8 ; Peptide Fragments ; Tap1 protein, mouse ; Brefeldin A (20350-15-6) ; Ovalbumin (9006-59-1) ; Ubiquitin Thiolesterase (EC 3.4.19.12)
Language	English
Publishing date	2012-12-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2012-08-447409
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Zs.MO 364: Show issues

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Article ; Online: Ubiquitin-dependent control of class II MHC localization is dispensable for antigen presentation and antibody production.

McGehee, Annette M / Strijbis, Karin / Guillen, Eduardo / Eng, Thomas / Kirak, Oktay / Ploegh, Hidde L

PloS one

2011 Volume 6, Issue 4, Page(s) e18817

Abstract: Controlled localization of class II MHC molecules is essential for proper class II MHC-restricted antigen presentation and the subsequent initiation of an adaptive immune response. Ubiquitination of class II MHC molecules on cytosolic lysine (K225) of ... ...

Abstract	Controlled localization of class II MHC molecules is essential for proper class II MHC-restricted antigen presentation and the subsequent initiation of an adaptive immune response. Ubiquitination of class II MHC molecules on cytosolic lysine (K225) of the β-chain has been shown to affect localization of the complex. We generated mice in which the endogenous β-chain locus is replaced with a GFP tagged mutant version that lacks the cytosolic lysine residue (I-A-β-K225R-EGFP). These mice have elevated levels of class II MHC as compared to I-A-β-EGFP mice, and immature bone marrow-derived dendritic cells show redistribution of class II MHC to the cell surface. Nonetheless, in these same cells efficiency of antigen presentation is unaffected in I-A-β-K225R-EGFP mice, as assayed for presentation of ovalbumin to appropriately specific T cells. The I-A-β-K225R-EGFP animals have normal CD4 T cell populations and are capable of generating antigen-specific antibody in response to model antigens and viral infection. We therefore conclude that in our experimental system modulation of trafficking by ubiquitination of residue K225 of the β-chain is not essential for the function of class II MHC products in antigen presentation or antibody production.
MeSH term(s)	Animals ; Antibody Formation ; Antigens/biosynthesis ; Green Fluorescent Proteins/genetics ; Histocompatibility Antigens Class II/metabolism ; Mice ; Mice, Inbred C57BL ; Mutation ; Ubiquitin/physiology
Chemical Substances	Antigens ; Histocompatibility Antigens Class II ; Ubiquitin ; enhanced green fluorescent protein ; Green Fluorescent Proteins (147336-22-9)
Language	English
Publishing date	2011-04-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0018817
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Article ; Online: RagA, but not RagB, is essential for embryonic development and adult mice.

Efeyan, Alejo / Schweitzer, Lawrence D / Bilate, Angelina M / Chang, Steven / Kirak, Oktay / Lamming, Dudley W / Sabatini, David M

Developmental cell

2014 Volume 29, Issue 3, Page(s) 321–329

Abstract: The mechanistic target of rapamycin complex 1 (mTORC1) integrates cues from growth factors and nutrients to control metabolism. In contrast to the growth factor input, genetic disruption of nutrient-dependent activation of mTORC1 in mammals remains ... ...

Abstract	The mechanistic target of rapamycin complex 1 (mTORC1) integrates cues from growth factors and nutrients to control metabolism. In contrast to the growth factor input, genetic disruption of nutrient-dependent activation of mTORC1 in mammals remains unexplored. We engineered mice lacking RagA and RagB genes, which encode the GTPases responsible for mTORC1 activation by nutrients. RagB has limited expression, and its loss shows no effects on mammalian physiology. RagA deficiency leads to E10.5 embryonic death, loss of mTORC1 activity, and severe growth defects. Primary cells derived from these mice exhibit no regulation of mTORC1 by nutrients and maintain high sensitivity to growth factors. Deletion of RagA in adult mice is lethal. Upon RagA loss, a myeloid population expands in peripheral tissues. RagA-specific deletion in liver increases cellular responses to growth factors. These results show the essentiality of nutrient sensing for mTORC1 activity in mice and its suppression of PI3K/Akt signaling.
MeSH term(s)	Animals ; Cell Line ; Embryo, Mammalian/embryology ; Hepatocytes/metabolism ; Liver/metabolism ; Mechanistic Target of Rapamycin Complex 1 ; Mice ; Mice, Knockout ; Monomeric GTP-Binding Proteins/genetics ; Monomeric GTP-Binding Proteins/metabolism ; Multiprotein Complexes/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction/genetics ; TOR Serine-Threonine Kinases/metabolism
Chemical Substances	Multiprotein Complexes ; RagA protein, mouse ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Monomeric GTP-Binding Proteins (EC 3.6.5.2) ; RagB protein, mouse (EC 3.6.5.2)
Language	English
Publishing date	2014-04-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2054967-2
ISSN	1878-1551 ; 1534-5807
ISSN (online)	1878-1551
ISSN	1534-5807
DOI	10.1016/j.devcel.2014.03.017
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Zs.A 5742: 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: Transnuclear mice with pre-defined T cell receptor specificities against Toxoplasma gondii obtained via SCNT.

Kirak, Oktay / Frickel, Eva-Maria / Grotenbreg, Gijsbert M / Suh, Heikyung / Jaenisch, Rudolf / Ploegh, Hidde L

Journal of visualized experiments : JoVE

2010 , Issue 43

Abstract: Lymphocytes, such as T cells, undergo genetic V(D)J recombination, to generate a receptor with a certain specificity. Mice transgenic for a rearranged antigen-specific T cell receptor (TCR) have been an indispensable tool to study T cell development and ... ...

Abstract	Lymphocytes, such as T cells, undergo genetic V(D)J recombination, to generate a receptor with a certain specificity. Mice transgenic for a rearranged antigen-specific T cell receptor (TCR) have been an indispensable tool to study T cell development and function. However, such TCRs are usually isolated from the relevant T cells after long-term culture often following repeated antigen stimulation, which unavoidably selects for T cells with high affinity. Random genomic integration of the TCR α- and β-chain and expression from non-endogenous promoters can lead to variations in expression level and kinetics. Epigenetic reprogramming via somatic cell nuclear transfer provides a tool to generate embryonic stem cells and mice from any cell of interest. Consequently, when SCNT is applied to T cells of known specificity, these genetic V(D)J rearrangements are transferred to the SCNT-embryonic stem cells (ESCs) and the mice derived from them, while epigenetic marks are reset. We have demonstrated that T cells with pre-defined specificities against Toxoplasma gondii can be used to generate mouse models that express the specific TCR from their endogenous loci, without experimentally introduced genetic modification. The relative ease and speed with which such transnuclear models can be obtained holds promise for the construction of other disease models.
MeSH term(s)	Animals ; Embryonic Stem Cells/immunology ; Epitopes, T-Lymphocyte/immunology ; Female ; Mice ; Nuclear Transfer Techniques ; Receptors, Antigen, T-Cell/immunology ; T-Lymphocytes/immunology ; Toxoplasma/immunology
Chemical Substances	Epitopes, T-Lymphocyte ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2010-09-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/2168
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