LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 39

Search options

  1. Article ; Online: Deciphering the antigen specificities of antibodies by clustering their complementarity determining region sequences.

    Saputri, Dianita S / Ismanto, Hendra S / Nugraha, Dendi K / Xu, Zichang / Horiguchi, Yasuhiko / Sakakibara, Shuhei / Standley, Daron M

    mSystems

    2023  Volume 8, Issue 6, Page(s) e0072223

    Abstract: Importance: Determining antigen and epitope specificity is an essential step in the discovery of therapeutic antibodies as well as in the analysis adaptive immune responses to disease or vaccination. Despite extensive efforts, deciphering antigen ... ...

    Abstract Importance: Determining antigen and epitope specificity is an essential step in the discovery of therapeutic antibodies as well as in the analysis adaptive immune responses to disease or vaccination. Despite extensive efforts, deciphering antigen specificity solely from BCR amino acid sequence remains a challenging task, requiring a combination of experimental and computational approaches. Here, we describe and experimentally validate a simple and straightforward approach for grouping antibodies that share antigen and epitope specificities based on their CDR sequence similarity. This approach allows us to identify the specificities of a large number of antibodies whose antigen targets are unknown, using a small fraction of antibodies with well-annotated binding specificities.
    MeSH term(s) Complementarity Determining Regions/genetics ; Antibodies/chemistry ; Antigens/chemistry ; Epitopes/chemistry ; Immunity ; Cluster Analysis
    Chemical Substances Complementarity Determining Regions ; Antibodies ; Antigens ; Epitopes
    Language English
    Publishing date 2023-11-17
    Publishing country United States
    Document type Journal Article
    ISSN 2379-5077
    ISSN (online) 2379-5077
    DOI 10.1128/msystems.00722-23
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  2. Article ; Online: Corrigendum to: Multiple tolerance checkpoints restrain affinity maturation of B cells expressing the germline precursor of a lupus patient-derived anti-dsDNA antibody in knock-in mice.

    El Hussien, Marwa Ali / Tsai, Chao-Yuan / Satouh, Yuhkoh / Motooka, Daisuke / Okuzaki, Daisuke / Ikawa, Masahito / Kikutani, Hitoshi / Sakakibara, Shuhei

    International immunology

    2022  Volume 34, Issue 4, Page(s) 225

    Language English
    Publishing date 2022-05-04
    Publishing country England
    Document type Published Erratum
    ZDB-ID 1013745-2
    ISSN 1460-2377 ; 0953-8178
    ISSN (online) 1460-2377
    ISSN 0953-8178
    DOI 10.1093/intimm/dxac007
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article ; Online: Contribution of viral mimics of cellular genes to KSHV infection and disease.

    Sakakibara, Shuhei / Tosato, Giovanna

    Viruses

    2014  Volume 6, Issue 9, Page(s) 3472–3486

    Abstract: Kaposi's sarcoma-associated herpesvirus (KSHV, also named Human herpesvirus 8 HHV-8) is the cause of Kaposi sarcoma (KS), the most common malignancy in HIV-infected individuals worldwide, primary effusion lymphoma (PEL) and multicentric Castleman disease ...

    Abstract Kaposi's sarcoma-associated herpesvirus (KSHV, also named Human herpesvirus 8 HHV-8) is the cause of Kaposi sarcoma (KS), the most common malignancy in HIV-infected individuals worldwide, primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). KSHV is a double-stranded DNA virus that encodes several homologues of cellular proteins. The structural similarity between viral and host proteins explains why some viral homologues function as their host counterparts, but sometimes at unusual anatomical sites and inappropriate times. In other cases, structural modification in the viral proteins can suppress or override the function of the host homologue, contributing to KSHV-related diseases. For example, viral IL-6 (vIL-6) is sufficiently different from human IL-6 to activate gp130 signaling independent of the α subunit. As a consequence, vIL-6 can activate many cell types that are unresponsive to cellular IL-6, contributing to MCD disease manifestations. Here, we discuss the molecular biology of KSHV homologues of cellular products as conduits of virus/host interaction with a focus on identifying new strategies for therapy of KS and other KSHV-related diseases.
    MeSH term(s) Castleman Disease/etiology ; Cytokines/genetics ; Cytokines/metabolism ; Herpesviridae Infections/complications ; Herpesviridae Infections/genetics ; Herpesviridae Infections/virology ; Herpesvirus 8, Human/genetics ; Humans ; Inflammation Mediators/metabolism ; Lymphoma, Primary Effusion/etiology ; NF-kappa B/metabolism ; Sarcoma, Kaposi/etiology ; Tumor Suppressor Protein p53/metabolism
    Chemical Substances Cytokines ; Inflammation Mediators ; NF-kappa B ; Tumor Suppressor Protein p53
    Language English
    Publishing date 2014-09-19
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v6093472
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  4. Article ; Online: Single-cell RNA-seq analysis identifies distinct myeloid cells in a case with encephalitis temporally associated with COVID-19 vaccination.

    Ishikawa, Masakazu / Shimada, Yuki / Ozono, Tatsuhiko / Matsumoto, Hisatake / Ogura, Hiroshi / Kihara, Keigo / Mochizuki, Hideki / Okuno, Tatsusada / Sakakibara, Shuhei / Kinoshita, Makoto / Okuzaki, Daisuke

    Frontiers in immunology

    2023  Volume 14, Page(s) 998233

    Abstract: Recently accumulating evidence has highlighted the rare occurrence of COVID-19 vaccination-induced inflammation in the central nervous system. However, the precise information on immune dysregulation related to the COVID-19 vaccination-associated ... ...

    Abstract Recently accumulating evidence has highlighted the rare occurrence of COVID-19 vaccination-induced inflammation in the central nervous system. However, the precise information on immune dysregulation related to the COVID-19 vaccination-associated autoimmunity remains elusive. Here we report a case of encephalitis temporally associated with COVID-19 vaccination, where single-cell RNA sequencing (scRNA-seq) analysis was applied to elucidate the distinct immune signature in the peripheral immune system. Peripheral blood mononuclear cells (PBMCs) were analyzed using scRNA-seq to clarify the cellular components of the patients in the acute and remission phases of the disease. The data obtained were compared to those acquired from a healthy cohort. The scRNA-seq analysis identified a distinct myeloid cell population in PBMCs during the acute phase of encephalitis. This specific myeloid population was detected neither in the remission phase of the disease nor in the healthy cohort. Our findings illustrate induction of a unique myeloid subset in encephalitis temporally associated with COVID-19 vaccination. Further research into the dysregulated immune signature of COVID-19 vaccination-associated autoimmunity including the cerebrospinal fluid (CSF) cells of central nervous system (CNS) is warranted to clarify the pathogenic role of the myeloid subset observed in our study.
    MeSH term(s) Humans ; COVID-19 Vaccines ; Leukocytes, Mononuclear ; Single-Cell Gene Expression Analysis ; COVID-19 ; Encephalitis ; Myeloid Cells ; Vaccination
    Chemical Substances COVID-19 Vaccines
    Language English
    Publishing date 2023-02-23
    Publishing country Switzerland
    Document type Case Reports ; Journal Article ; 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.2023.998233
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  5. Article ; Online: Opposing roles of RUBCN isoforms in autophagy and memory B cell generation.

    Tsai, Chao-Yuan / Sakakibara, Shuhei / Kuan, Yu-Diao / Omori, Hiroko / El Hussien, Maruwa Ali / Okuzaki, Daisuke / Lu, Shiou-Ling / Noda, Takeshi / Tabata, Keisuke / Nakamura, Shuhei / Yoshimori, Tamotsu / Kikutani, Hitoshi

    Science signaling

    2023  Volume 16, Issue 803, Page(s) eade3599

    Abstract: RUBCN (also known as Rubicon) was originally identified as a negative regulator of autophagy, a process by which cells degrade and recycle damaged components or organelles and that requires the activity of the class III PI3K VPS34 and the mTORC1 protein ... ...

    Abstract RUBCN (also known as Rubicon) was originally identified as a negative regulator of autophagy, a process by which cells degrade and recycle damaged components or organelles and that requires the activity of the class III PI3K VPS34 and the mTORC1 protein complex. Here, we characterized the role of a shorter isoform, RUBCN
    MeSH term(s) Memory B Cells ; B-Lymphocytes ; Autophagy ; Protein Isoforms/genetics ; Mechanistic Target of Rapamycin Complex 1/genetics
    Chemical Substances Protein Isoforms ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1)
    Language English
    Publishing date 2023-09-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2417226-1
    ISSN 1937-9145 ; 1945-0877
    ISSN (online) 1937-9145
    ISSN 1945-0877
    DOI 10.1126/scisignal.ade3599
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  6. Article ; Online: Multiple tolerance checkpoints restrain affinity maturation of B cells expressing the germline precursor of a lupus patient-derived anti-dsDNA antibody in knock-in mice.

    El Hussien, Marwa Ali / Tsai, Chao-Yuan / Satouh, Yuhkoh / Motooka, Daisuke / Okuzaki, Daisuke / Ikawa, Masahito / Kikutani, Hitoshi / Sakakibara, Shuhei

    International immunology

    2021  Volume 34, Issue 4, Page(s) 207–223

    Abstract: Anti-dsDNA antibodies are a hallmark of systemic lupus erythematosus and are highly associated with its exacerbation. Cumulative evidence has suggested that somatic hypermutation contributes to the high-affinity reactivity of anti-dsDNA antibodies. Our ... ...

    Abstract Anti-dsDNA antibodies are a hallmark of systemic lupus erythematosus and are highly associated with its exacerbation. Cumulative evidence has suggested that somatic hypermutation contributes to the high-affinity reactivity of anti-dsDNA antibodies. Our previous study demonstrated that these antibodies are generated from germline precursors with low-affinity ssDNA reactivity through affinity maturation and clonal expansion in patients with acute lupus. This raised the question of whether such precursors could be subjected to immune tolerance. To address this, we generated a site-directed knock-in (KI) mouse line, G9gl, which carries germline-reverted sequences of the VH-DH-JH and Vκ-Jκ regions of patient-derived, high-affinity anti-dsDNA antibodies. G9gl heterozygous mice had a reduced number of peripheral B cells, only 27% of which expressed G9gl B-cell receptor (BCR). The remaining B cells harbored non-KI allele-derived immunoglobulin heavy (IgH) chains or fusion products of upstream mouse VH and the KI gene, suggesting that receptor editing through VH replacement occurred in a large proportion of B cells in the KI mice. G9gl BCR-expressing B cells responded to ssDNA but not dsDNA, and exhibited several anergic phenotypes, including reduced surface BCR and shortened life span. Furthermore, G9gl B cells were excluded from germinal centers (GCs) induced by several conditions. In particular, following immunization with methylated bovine serum albumin-conjugated bacterial DNA, G9gl B cells occurred at a high frequency in memory B cells but not GC B cells or plasmablasts. Collectively, multiple tolerance checkpoints prevented low-affinity precursors of pathogenic anti-dsDNA B cells from undergoing clonal expansion and affinity maturation in GCs.
    MeSH term(s) Animals ; Antibodies, Antinuclear ; B-Lymphocytes ; Germ Cells ; Humans ; Immune Tolerance/genetics ; Immunoglobulin Heavy Chains/genetics ; Lupus Erythematosus, Systemic/genetics ; Mice ; Receptors, Antigen, B-Cell
    Chemical Substances Antibodies, Antinuclear ; Immunoglobulin Heavy Chains ; Receptors, Antigen, B-Cell ; anti-dsDNA autoantibody
    Language English
    Publishing date 2021-12-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1013745-2
    ISSN 1460-2377 ; 0953-8178
    ISSN (online) 1460-2377
    ISSN 0953-8178
    DOI 10.1093/intimm/dxab111
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  7. Article ; Online: Local production of broadly cross-reactive IgE against multiple fungal cell wall polysaccharides in patients with allergic fungal rhinosinusitis.

    Haruna, Soichiro / Takeda, Kazuya / El-Hussien, Marwa Ali / Maeda, Yohei / Hayama, Masaki / Shikina, Takashi / Doi, Katsumi / Inohara, Hidenori / Kikutani, Hitoshi / Sakakibara, Shuhei

    Allergy

    2022  Volume 77, Issue 10, Page(s) 3147–3151

    MeSH term(s) Cell Wall ; Chronic Disease ; Fungal Polysaccharides ; Humans ; Immunoglobulin E ; Rhinitis, Allergic ; Sinusitis/microbiology
    Chemical Substances Fungal Polysaccharides ; Immunoglobulin E (37341-29-0)
    Language English
    Publishing date 2022-06-27
    Publishing country Denmark
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 391933-x
    ISSN 1398-9995 ; 0105-4538
    ISSN (online) 1398-9995
    ISSN 0105-4538
    DOI 10.1111/all.15413
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  8. Article ; Online: Viral interleukin-6: role in Kaposi's sarcoma-associated herpesvirus: associated malignancies.

    Sakakibara, Shuhei / Tosato, Giovanna

    Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research

    2011  Volume 31, Issue 11, Page(s) 791–801

    Abstract: Viral interleukin-6 (vIL-6) is a product of Kaposi's sarcoma-associated herpesvirus (KSHV) expressed in latently infected cells and to a higher degree during viral replication. A distinctive feature of vIL-6 is the ability to directly bind and activate ... ...

    Abstract Viral interleukin-6 (vIL-6) is a product of Kaposi's sarcoma-associated herpesvirus (KSHV) expressed in latently infected cells and to a higher degree during viral replication. A distinctive feature of vIL-6 is the ability to directly bind and activate gp130 signaling in the absence of other receptor subunits. Secretion of vIL-6 is generally poor, but vIL-6 can activate gp130 from inside the cell. Due to the wide cell distribution of gp130, vIL-6 has the potential to induce a wide range of biological effects. Expression of vIL-6 is variable in KSHV-associated Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), multicentric Castleman's disease (MCD), and in a newly described MCD-like systemic inflammatory syndrome observed in human immunodeficiency virus-positive patients. PEL effusions usually contain vIL-6 at high concentrations; since vIL-6 induces vascular endothelial growth factor, vIL-6 likely contributes to vascular permeability and formation of PEL effusions. Lymph nodes affected with MCD contain vIL-6-positive cells, and vIL-6 levels rise in conjunction with flares of the disease and likely contribute to symptoms of inflammation. The development of vIL-6 inhibitors is a potentially important advance in the treatment of KSHV-associated malignancies where vIL-6 is expressed.
    MeSH term(s) Animals ; Castleman Disease/metabolism ; Castleman Disease/pathology ; Castleman Disease/virology ; Herpesvirus 8, Human/genetics ; Herpesvirus 8, Human/metabolism ; Humans ; Interleukin-6/genetics ; Interleukin-6/metabolism ; Lymphoma, Primary Effusion/metabolism ; Lymphoma, Primary Effusion/pathology ; Lymphoma, Primary Effusion/virology ; Sarcoma, Kaposi/metabolism ; Sarcoma, Kaposi/pathology ; Sarcoma, Kaposi/virology
    Chemical Substances Interleukin-6
    Language English
    Publishing date 2011-07-18
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 1226675-9
    ISSN 1557-7465 ; 1079-9907
    ISSN (online) 1557-7465
    ISSN 1079-9907
    DOI 10.1089/jir.2011.0043
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  9. Article ; Online: Bystander inhibition of humoral immune responses by Epstein-Barr virus LMP1.

    Tsai, Chao-Yuan / Sakakibara, Shuhei / Yasui, Teruhito / Minamitani, Takeharu / Okuzaki, Daisuke / Kikutani, Hitoshi

    International immunology

    2018  Volume 30, Issue 12, Page(s) 579–590

    Abstract: Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1), which mimics a constitutively active receptor, is required for viral transformation of primary B cells. LMP1 is expressed in EBV-infected germinal center (GC) B cells of immunocompetent ... ...

    Abstract Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1), which mimics a constitutively active receptor, is required for viral transformation of primary B cells. LMP1 is expressed in EBV-infected germinal center (GC) B cells of immunocompetent individuals, suggesting that it may contribute to persistent EBV infection. In this study, we generated and analyzed mice that expressed LMP1 under the control of the CD19 or activation-induced cytidine deaminase (AID) promoter. Expression of LMP1 induced activation of B cells but severely inhibited their differentiation into antibody-secreting cells (ASCs) in vitro and GC B cells in vivo. LMP1-expressing (LMP1+) B cells not only suppressed the functions of wild-type (WT) B cells in in vitro co-culture, but also blocked differentiation of WT B cells into GC B cells and ASCs in immunized bone marrow chimeric mice. Microarray analysis revealed that the gene encoding indoleamine 2,3-dioxygenase 1 (IDO1), a major enzyme involved in the tryptophan metabolic process, was highly induced by LMP1. Either inhibition of IDO1 activity by methyl-l-tryptophan or knockout of Ido1 in LMP1+ B cells could rescue WT B cells from such suppression. IDO1-induced tryptophan consumption and production of tryptophan metabolites appeared to be responsible for inhibition of B-cell function. We conclude that LMP1 expression in antigen-committed B cells not only directly impairs GC B-cell differentiation, but also indirectly inhibits the functions of neighboring B cells, resulting in suppression of humoral immune responses. Such bystander inhibition by LMP1+ B cells may contribute to immune evasion by EBV.
    MeSH term(s) Animals ; B-Lymphocytes/immunology ; Cell Differentiation ; Herpesvirus 4, Human/immunology ; Immunity, Humoral/immunology ; Mice ; Mice, Transgenic ; Viral Matrix Proteins/immunology
    Chemical Substances EBV-associated membrane antigen, Epstein-Barr virus ; Viral Matrix Proteins
    Language English
    Publishing date 2018-09-24
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1013745-2
    ISSN 1460-2377 ; 0953-8178
    ISSN (online) 1460-2377
    ISSN 0953-8178
    DOI 10.1093/intimm/dxy053
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  10. Article ; Online: Antibody feedback contributes to facilitating the development of Omicron-reactive memory B cells in SARS-CoV-2 mRNA vaccinees.

    Inoue, Takeshi / Shinnakasu, Ryo / Kawai, Chie / Yamamoto, Hiromi / Sakakibara, Shuhei / Ono, Chikako / Itoh, Yumi / Terooatea, Tommy / Yamashita, Kazuo / Okamoto, Toru / Hashii, Noritaka / Ishii-Watabe, Akiko / Butler, Noah S / Matsuura, Yoshiharu / Matsumoto, Hisatake / Otsuka, Shinya / Hiraoka, Kei / Teshima, Takanori / Murakami, Masaaki /
    Kurosaki, Tomohiro

    The Journal of experimental medicine

    2022  Volume 220, Issue 2

    Abstract: In contrast to a second dose of the SARS-CoV-2 mRNA vaccine, a third dose elicits potent neutralizing activity against the Omicron variant. To address the underlying mechanism for this differential antibody response, we examined spike receptor-binding ... ...

    Abstract In contrast to a second dose of the SARS-CoV-2 mRNA vaccine, a third dose elicits potent neutralizing activity against the Omicron variant. To address the underlying mechanism for this differential antibody response, we examined spike receptor-binding domain (RBD)-specific memory B cells in vaccinated individuals. Frequency of Omicron-reactive memory B cells increased ∼9 mo after the second vaccine dose. These memory B cells show an altered distribution of epitopes from pre-second memory B cells, presumably due to an antibody feedback mechanism. This hypothesis was tested using mouse models, showing that an addition or a depletion of RBD-induced serum antibodies results in a concomitant increase or decrease, respectively, of Omicron-reactive germinal center (GC) and memory B cells. Our data suggest that pre-generated antibodies modulate the selection of GC and subsequent memory B cells after the second vaccine dose, accumulating more Omicron-reactive memory B cells over time, which contributes to the generation of Omicron-neutralizing antibodies elicited by the third vaccine dose.
    MeSH term(s) Animals ; Mice ; Humans ; COVID-19 Vaccines ; Feedback ; Memory B Cells ; SARS-CoV-2 ; COVID-19/prevention & control ; RNA, Messenger ; Antibodies, Neutralizing ; Antibodies, Viral
    Chemical Substances COVID-19 Vaccines ; RNA, Messenger ; Antibodies, Neutralizing ; Antibodies, Viral
    Language English
    Publishing date 2022-12-13
    Publishing country United States
    Document type 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.20221786
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

To top