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Artikel ; Online: Systematic memory B cell archiving and random display shape the human splenic marginal zone throughout life.

Kibler, Artur / Budeus, Bettina / Homp, Ekaterina / Bronischewski, Kevin / Berg, Victoria / Sellmann, Ludger / Murke, Florian / Heinold, Andreas / Heinemann, Falko M / Lindemann, Monika / Bekeredjian-Ding, Isabelle / Horn, Peter A / Kirschning, Carsten J / Küppers, Ralf / Seifert, Marc

The Journal of experimental medicine

2021 Band 218, Heft 4

Abstract: Human memory B cells (MBCs) are generated and diversified in secondary lymphoid tissues ...

Abstract	Human memory B cells (MBCs) are generated and diversified in secondary lymphoid tissues throughout the organism. A paired immunoglobulin (Ig)-gene repertoire analysis of peripheral blood (PB) and splenic MBCs from infant, adult, and elderly humans revealed that throughout life, circulating MBCs are comprehensively archived in the spleen. Archive MBC clones are systematically preserved and uncoupled from class-switching. Clonality in the spleen increases steadily, but boosts at midlife, thereby outcompeting small clones. The splenic marginal zone (sMZ) represents a primed MBC compartment, generated from a stochastic exchange within the archive memory pool. This is supported by functional assays, showing that PB and splenic CD21+ MBCs acquire transient CD21high expression upon NOTCH2-stimulation. Our study provides insight that the human MBC system in PB and spleen is composed of three interwoven compartments: the dynamic relationship of circulating, archive, and its subset of primed (sMZ) memory changes with age, thereby contributing to immune aging.
Mesh-Begriff(e)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aging/immunology ; Animals ; B-Lymphocytes/immunology ; Biopsy ; Blood Donors ; Cell Line ; Child ; Child, Preschool ; Coculture Techniques ; Female ; Humans ; Immunologic Memory ; Infant ; Infant, Newborn ; Male ; Mesenchymal Stem Cells/metabolism ; Mice ; Middle Aged ; Phenotype ; Receptors, Complement 3d/metabolism ; Spleen/immunology ; Spleen/pathology ; Young Adult
Chemische Substanzen	Receptors, Complement 3d
Sprache	Englisch
Erscheinungsdatum	2021-03-23
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20201952
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Humoral and Cellular Responses to a Single Dose of Fendrix in Renal Transplant Recipients with Non-response to Previous Hepatitis B Vaccination.

Lindemann, M / Zaslavskaya, M / Fiedler, M / Wilde, B / Heinemann, F M / Heinold, A / Horn, P A / Witzke, O

Scandinavian journal of immunology

2017 Band 85, Heft 1, Seite(n) 51–57

Abstract: Approximately 70% of kidney transplant recipients are non-responders to conventional hepatitis B ...

Abstract	Approximately 70% of kidney transplant recipients are non-responders to conventional hepatitis B virus (HBV) vaccines. We examined whether Fendrix™, an HBV vaccine containing 3-O-desacyl-4'-monophosphoryl lipid A (MPL) as adjuvant, could induce HBV immunity in these patients and compared their vaccination efficacy with healthy controls tested previously by the same assays. We selected 35 kidney transplant recipients who had been vaccinated at least thrice against HBV but had never displayed anti-HBs antibodies. We re-assessed their anti-HBs antibody titres and further determined cellular HBV immunity by proliferation assay and interferon (IFN)-γ ELISpot. Seventeen recipients did neither display humoral nor cellular immunity and could be tested prior to and at month 1 after vaccination. Of note, HLA antigens associated with non-response to HBV vaccination (HLA-DRB103 and HLA-DQB102) were over-represented in these 17 recipients. At month 1 after a single vaccination with Fendrix™, we observed a significant increase in anti-HBs antibodies (P = 0.02). In seven of 17 recipients, we detected anti-HBs antibodies ≥10 IU/l (10-264), in four HBV-specific lymphocyte proliferation (stimulation index of 2.6-8.7) and in one specific IFN-γ responses (12 spots increment). The vaccination response to Fendrix™ was significantly higher (P = 0.035) than the response to HBVaxPro™ in young healthy controls. In summary, the results show that a single vaccination with Fendrix
Mesh-Begriff(e)	Adult ; Aged ; Antibodies, Viral/blood ; Cell Proliferation ; Cells, Cultured ; Enzyme-Linked Immunospot Assay ; Female ; Hepatitis B/immunology ; Hepatitis B/prevention & control ; Hepatitis B Antibodies/immunology ; Hepatitis B Vaccines/immunology ; Humans ; Immune Tolerance ; Immunity, Cellular ; Immunity, Humoral ; Interferon-gamma/metabolism ; Kidney Transplantation ; Male ; Vaccination ; Young Adult
Chemische Substanzen	Antibodies, Viral ; Fendrix ; Hepatitis B Antibodies ; Hepatitis B Vaccines ; Interferon-gamma (82115-62-6)
Sprache	Englisch
Erscheinungsdatum	2017-01
Erscheinungsland	England
Dokumenttyp	Journal Article
ZDB-ID	120476-2
ISSN	1365-3083 ; 0300-9475
ISSN (online)	1365-3083
ISSN	0300-9475
DOI	10.1111/sji.12497
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Amino Acid Substitutions within HLA-B*27-Restricted T Cell Epitopes Prevent Recognition by Hepatitis Delta Virus-Specific CD8

Karimzadeh, Hadi / Kiraithe, Muthamia M / Kosinska, Anna D / Glaser, Manuel / Fiedler, Melanie / Oberhardt, Valerie / Salimi Alizei, Elahe / Hofmann, Maike / Mok, Juk Yee / Nguyen, Melanie / van Esch, Wim J E / Budeus, Bettina / Grabowski, Jan / Homs, Maria / Olivero, Antonella / Keyvani, Hossein / Rodríguez-Frías, Francisco / Tabernero, David / Buti, Maria /

Heinold, Andreas / Alavian, Seyed Moayed / Bauer, Tanja / Schulze Zur Wiesch, Julian / Raziorrouh, Bijan / Hoffmann, Daniel / Smedile, Antonina / Rizzetto, Mario / Wedemeyer, Heiner / Timm, Jörg / Antes, Iris / Neumann-Haefelin, Christoph / Protzer, Ulrike / Roggendorf, Michael

Journal of virology

2018 Band 92, Heft 13

Abstract: Virus-specific CD8 T cell response seems to play a significant role in the outcome of hepatitis delta virus (HDV) infection. However, the HDV-specific T cell epitope repertoire and mechanisms of CD8 T cell failure in HDV infection have been poorly ... ...

Abstract	Virus-specific CD8 T cell response seems to play a significant role in the outcome of hepatitis delta virus (HDV) infection. However, the HDV-specific T cell epitope repertoire and mechanisms of CD8 T cell failure in HDV infection have been poorly characterized. We therefore aimed to characterize HDV-specific CD8 T cell epitopes and the impacts of viral mutations on immune escape. In this study, we predicted peptide epitopes binding the most frequent human leukocyte antigen (HLA) types and assessed their HLA binding capacities. These epitopes were characterized in HDV-infected patients by intracellular gamma interferon (IFN-γ) staining. Sequence analysis of large hepatitis delta antigen (L-HDAg) and HLA typing were performed in 104 patients. The impacts of substitutions within epitopes on the CD8 T cell response were evaluated experimentally and by
Mesh-Begriff(e)	Amino Acid Sequence ; Amino Acid Substitution ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Epitopes, T-Lymphocyte/immunology ; Epitopes, T-Lymphocyte/metabolism ; HLA-B Antigens/genetics ; HLA-B Antigens/immunology ; HLA-B Antigens/metabolism ; Hepatitis D/genetics ; Hepatitis D/immunology ; Hepatitis D/virology ; Hepatitis Delta Virus/genetics ; Hepatitis Delta Virus/immunology ; Hepatitis delta Antigens/immunology ; Hepatitis delta Antigens/metabolism ; Humans ; Mutation ; Sequence Homology
Chemische Substanzen	Epitopes, T-Lymphocyte ; HLA-B Antigens ; Hepatitis delta Antigens ; hepatitis delta virus large antigen
Sprache	Englisch
Erscheinungsdatum	2018-06-13
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.01891-17
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Adaptation of the hepatitis B virus core protein to CD8(+) T-cell selection pressure.

Kefalakes, Helenie / Budeus, Bettina / Walker, Andreas / Jochum, Christoph / Hilgard, Gudrun / Heinold, Andreas / Heinemann, Falko M / Gerken, Guido / Hoffmann, Daniel / Timm, Joerg

Hepatology (Baltimore, Md.)

2015 Band 62, Heft 1, Seite(n) 47–56

Abstract: Unlabelled: Activation of hepatitis B virus (HBV)-specific CD8 T cells by therapeutic vaccination ... the human leukocyte antigen (HLA) class I genotype (A and B loci) was determined. Residues under selection ...

Abstract	Unlabelled: Activation of hepatitis B virus (HBV)-specific CD8 T cells by therapeutic vaccination may promote sustained control of viral replication by clearance of covalently closed circular DNA from infected hepatocytes. However, little is known about the exact targets of the CD8 T-cell response and whether HBV reproducibly evades CD8 T-cell immune pressure by mutation. The aim of this study was to address if HBV reproducibly selects substitutions in CD8 T-cell epitopes that functionally act as immune escape mutations. The HBV core gene was amplified and sequenced from 148 patients with chronic HBV infection, and the human leukocyte antigen (HLA) class I genotype (A and B loci) was determined. Residues under selection pressure in the presence of particular HLA class I alleles were identified by a statistical approach utilizing the novel analysis package SeqFeatR. With this approach we identified nine residues in HBV core under selection pressure in the presence of 10 different HLA class I alleles. Additional immunological experiments confirmed that seven of the residues were located inside epitopes targeted by patients with chronic HBV infection carrying the relevant HLA class I allele. Consistent with viral escape, the selected substitutions reproducibly impaired recognition by HBV-specific CD8 T cells. Conclusion: Viral sequence analysis allows identification of HLA class I-restricted epitopes under reproducible selection pressure in HBV core; the possibility of viral escape from CD8 T-cell immune pressure needs attention in the context of therapeutic vaccination against HBV.
Mesh-Begriff(e)	Adaptation, Biological ; CD8-Positive T-Lymphocytes/physiology ; Epitopes, T-Lymphocyte ; Genes, MHC Class I ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/immunology ; Hepatitis B, Chronic/virology ; Humans ; Selection, Genetic ; Viral Core Proteins/genetics
Chemische Substanzen	Epitopes, T-Lymphocyte ; Viral Core Proteins
Sprache	Englisch
Erscheinungsdatum	2015-07
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604603-4
ISSN	1527-3350 ; 0270-9139
ISSN (online)	1527-3350
ISSN	0270-9139
DOI	10.1002/hep.27771
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Air pollution trapping in the Dresden Basin from gray-zone scale urban modeling

M. Weger / B. Heinold

Atmospheric Chemistry and Physics, Vol 23, Pp 13769-

2023 Band 13790

Abstract: The microscale variability of urban air pollution is essentially driven by the interaction between meteorology and urban topography, which remains challenging to represent spatially accurately and computationally efficiently in urban dispersion models. ... ...

Abstract	The microscale variability of urban air pollution is essentially driven by the interaction between meteorology and urban topography, which remains challenging to represent spatially accurately and computationally efficiently in urban dispersion models. Natural topography can additionally exert a considerable amplifying effect on urban background pollution, depending on atmospheric stability. This requires an equally important representation in models, as even subtle terrain-height variations can enforce characteristic local flow regimes. In this model study, the effects of urban and natural topography on the local winds and air pollution dispersion in the Dresden Basin in the Eastern German Elbe valley are investigated. A new, efficient urban microscale model is used within a multiscale air quality modeling framework. The simulations that consider real meteorological and emission conditions focus on two periods in late winter and early summer, respectively, as well as on black carbon (BC), a key air pollutant mainly emitted from motorized traffic. As a complement to the commonly used mass concentrations, the particle age content (age concentration) is simulated. This concept, which was originally developed to study hydrological reservoir flows in a Eulerian framework, is adapted here for the first time for atmospheric boundary-layer modeling. The approach is used to identify stagnant or recirculating orographic air flows and resulting air pollution trapping. An empirical orthogonal function (EOF) analysis is applied to the simulation results to attribute the air pollution modes to specific weather patterns and quantify their significance. Air quality monitoring data for the region are used for model evaluation. The model results show a strong sensitivity to atmospheric conditions, but generally confirm increased BC levels in Dresden due to the valley location. The horizontal variability of mass concentrations is dominated by the patterns of traffic emissions, which overlay potential orography-driven pollutant ...
Schlagwörter	Physics ; QC1-999 ; Chemistry ; QD1-999
Thema/Rubrik (Code)	333
Sprache	Englisch
Erscheinungsdatum	2023-11-01T00:00:00Z
Verlag	Copernicus Publications
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel ; Konferenzbeitrag: Viral sequence analysis of the hepatitis B virus core protein reveals CD8 T cell epitopes under reproducible selection pressure

Kefalakes, H / Budeus, B / Walker, A / Jochum, C / Hilgard, G / Heinold, A / Heinemann, F / Gerken, G / Hoffmann, D / Timm, J

Zeitschrift für Gastroenterologie

2015

Abstract: Background: Chronic infections with the hepatitis B virus (HBV) are worldwide an enormous ... infection and the HLA class I genotype (A and B locus) was determined. Residues under selection pressure ...

Veranstaltung/Kongress	31. Jahrestagung der Deutschen Arbeitsgemeinschaft zum Studium der Leber, München, 2015
Abstract	Background: Chronic infections with the hepatitis B virus (HBV) are worldwide an enormous public health problem. Effective suppression of viral replication can be achieved with inhibitors of the viral polymerase, however, in most cases lifelong treatment is required to avoid recurrence of viremia. Activation of HBV-specific CD8 T cells by therapeutic vaccination may promote sustained control of viral replication by clearance of cccDNA from infected hepatocytes. Importantly, little is known about the exact targets of the CD8 T cell response and the extent of selection pressure on the virus. Here, it was hypothesized that CD8 T cell responses associated with strong selection pressure on the virus can be identified by viral sequence analysis. Methods: The HBV core gene was amplified and sequenced from 148 patients with chronic HBV infection and the HLA class I genotype (A and B locus) was determined. Residues under selection pressure in the presence of particular HLA class I alleles were identified by a statistical approach utilizing a novel analysis package 'SeqFeatR'. Candidate CD8 T cell epitopes were confirmed by analysis of PBMCs from patients with chronic and acute infection. Results: With a false discovery rate set to 0.2 a total of 9 residues under selection pressure in the presence of 10 different HLA class I alleles were identified. Additional immunological experiments confirmed that 7 of the residues were located inside previously unidentified epitopes targeted in patients with chronic HBV infection carrying the relevant HLA class I allele. Consistent with viral escape some of the selected substitutions impaired recognition by HBV-specific CD8 T cells. Conclusion: Viral sequence analysis allows identification of HLA class I-restricted epitopes under reproducible selection pressure in HBV core. The possibility of viral adaptation to CD8 T cell immune pressure needs attention in the context of therapeutic vaccination. Corresponding author: Kefalakes, Helenie E-Mail: helenie.kefalakes@uk-essen.de
Sprache	Englisch
Erscheinungsdatum	2015-01-16
Erscheinungsort	Stuttgart ; New York
Dokumenttyp	Artikel ; Konferenzbeitrag
ZDB-ID	201387-3
ISSN	1439-7803 ; 0044-2771 ; 0172-8504
ISSN (online)	1439-7803
ISSN	0044-2771 ; 0172-8504
DOI	10.1055/s-0034-1397260
Datenquelle	Thieme Verlag

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Artikel: Characterization of a new HLA-B allele, HLA-B5312, and re-evaluation of the published sequences of the untranslated regions of HLA-B35 and HLA-B*53.

Heinold, A / Bauer, M / Scherer, S / Opelz, G / Tran, T H

Tissue antigens

2007 Band 70, Heft 4, Seite(n) 319–323

Abstract: We report a novel human leukocyte antigen (HLA)-B allele, HLA-B*5312. Compared with HLA-B*530101 ... version 2.16.0, January 2007), we found that HLA-B*530101 had a C instead of a T at nucleotide -221 ... whereas HLA-B*350101 had a C instead of an A at nucleotide 2992. According to our sequencing results, HLA-B*5312 ...

Abstract	We report a novel human leukocyte antigen (HLA)-B allele, HLA-B5312. Compared with HLA-B530101, there is one silent substitution at nucleotide 438 and two non-synonymous substitutions at nucleotides 431 and 440, causing a change of the amino acid sequence (Asn-->Ser at codon 77 and Ile-->Thr at codon 80, respectively) within the Bw4 epitope. In contrast to the published sequences (IMGT/HLA Database, version 2.16.0, January 2007), we found that HLA-B530101 had a C instead of a T at nucleotide -221, whereas HLA-B350101 had a C instead of an A at nucleotide 2992. According to our sequencing results, HLA-B5312 resembles HLA-B350101 regarding its sequence of the untranslated regions. HLA-B5312 may have been the result of a double crossing over event during which HLA-B350101 adopted a Bw4 motif.
Mesh-Begriff(e)	Alleles ; Base Sequence ; HLA-B Antigens/genetics ; Humans ; Molecular Sequence Data ; Untranslated Regions
Chemische Substanzen	HLA-B Antigens ; Untranslated Regions
Sprache	Englisch
Erscheinungsdatum	2007-10
Erscheinungsland	England
Dokumenttyp	Journal Article
ZDB-ID	120440-3
ISSN	1399-0039 ; 0001-2815
ISSN (online)	1399-0039
ISSN	0001-2815
DOI	10.1111/j.1399-0039.2007.00900.x
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Characterization of four new HLA alleles: HLA-B15:01:18, HLA-B44:110, HLA-C04:01:22 and HLA-DQB 105:14.

Heyder, J / Heinold, A / Fiedler, G / Opelz, G / Tran, T H

Tissue antigens

2012 Band 79, Heft 3, Seite(n) 209–210

Abstract: We describe four novel HLA alleles, HLA-B*15:01:18, HLA-B*44:110, HLA-C*04:01:22 and HLA-DQB1*05:14. ...

Abstract	We describe four novel HLA alleles, HLA-B15:01:18, HLA-B44:110, HLA-C04:01:22 and HLA-DQB105:14.
Mesh-Begriff(e)	Alleles ; Base Sequence ; HLA Antigens/classification ; HLA Antigens/genetics ; HLA-B Antigens/genetics ; HLA-C Antigens/genetics ; HLA-DQ beta-Chains/genetics ; Humans ; Molecular Sequence Data ; Sequence Alignment
Chemische Substanzen	HLA Antigens ; HLA-B Antigens ; HLA-C Antigens ; HLA-DQ beta-Chains ; HLA-DQB1 antigen
Sprache	Englisch
Erscheinungsdatum	2012-03
Erscheinungsland	England
Dokumenttyp	Journal Article
ZDB-ID	120440-3
ISSN	1399-0039 ; 0001-2815
ISSN (online)	1399-0039
ISSN	0001-2815
DOI	10.1111/j.1399-0039.2011.01805.x
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Buch ; Online: Air pollution trapping in the Dresden Basin from gray-zone scale urban modeling

Weger, Michael / Heinold, Bernd

eISSN: 1680-7324

2023

Abstract	The microscale variability of urban air pollution is essentially driven by the interaction between meteorology and urban topography, which remains challenging to represent spatially accurately and computationally efficiently in urban dispersion models. Natural topography can additionally exert a considerable amplifying effect on urban background pollution, depending on atmospheric stability. This requires an equally important representation in models, as even subtle terrain-height variations can enforce characteristic local flow regimes. In this model study, the effects of urban and natural topography on the local winds and air pollution dispersion in the Dresden Basin in the Eastern German Elbe valley are investigated. A new, efficient urban microscale model is used within a multiscale air quality modeling framework. The simulations that consider real meteorological and emission conditions focus on two periods in late winter and early summer, respectively, as well as on black carbon (BC), a key air pollutant mainly emitted from motorized traffic. As a complement to the commonly used mass concentrations, the particle age content (age concentration) is simulated. This concept, which was originally developed to study hydrological reservoir flows in a Eulerian framework, is adapted here for the first time for atmospheric boundary-layer modeling. The approach is used to identify stagnant or recirculating orographic air flows and resulting air pollution trapping. An empirical orthogonal function (EOF) analysis is applied to the simulation results to attribute the air pollution modes to specific weather patterns and quantify their significance. Air quality monitoring data for the region are used for model evaluation. The model results show a strong sensitivity to atmospheric conditions, but generally confirm increased BC levels in Dresden due to the valley location. The horizontal variability of mass concentrations is dominated by the patterns of traffic emissions, which overlay potential orography-driven pollutant ...
Thema/Rubrik (Code)	333
Sprache	Englisch
Erscheinungsdatum	2023-11-06
Erscheinungsland	de
Dokumenttyp	Buch ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Buch ; Online: Radiative cooling and atmospheric perturbation effects of dust aerosol from the Aralkum Desert in Central Asia

Banks, Jamie R. / Heinold, Bernd / Schepanski, Kerstin

eISSN:

2023

Abstract: The Aralkum is a new desert created by the desiccation of the Aral Sea since the 1960s, and is an efﬁcient source of dust aerosol which may perturb the regional Central Asian radiation balance. COSMO-MUSCAT model simulations are used to quantify the ... ...

Abstract	The Aralkum is a new desert created by the desiccation of the Aral Sea since the 1960s, and is an efﬁcient source of dust aerosol which may perturb the regional Central Asian radiation balance. COSMO-MUSCAT model simulations are used to quantify the direct radiative effects (DREs) of Aralkum dust, and investigate the associated perturbations to the atmospheric environment. Considering scenarios of ‘Past’ and ‘Present’ deﬁned by differences in surface water coverage, it is found that in the Present scenario the yearly mean net surface DRE across the Aralkum is -1.34±6.19 W m -2 , of which -0.15±1.19 W m -2 comes from dust emitted by the Aralkum. Meanwhile in the atmosphere the yearly mean DRE is -0.62±2.91 W m -2 , of which -0.05±0.51 W m -2 comes from Aralkum dust: on the yearly timescale Aralkum dust is cooling both at the surface and in the atmosphere. The daytime surface cooling effect (solar zenith angle ≲70–80°) outweighs both the nighttime heating effect and the corresponding atmospheric daytime (solar zenith angle ≲60–70°) heating and nighttime cooling effects. Instantaneous Aralkum dust DREs contribute up to -116 W m -2 of surface cooling and +54 W m -2 of atmospheric heating. Aralkum dust perturbs the surface pressure in the vicinity of the Aralkum by up to +0.76 Pa on the monthly timescale, implying a strengthening of the Siberian High in winter and a weakening of the Central Asian Heat Low in summer.
Thema/Rubrik (Code)	333
Sprache	Englisch
Erscheinungsdatum	2023-12-05
Erscheinungsland	de
Dokumenttyp	Buch ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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