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  1. Article ; Online: Tuning up T-cell receptors.

    Rappazzo, C Garrett / Birnbaum, Michael E

    Nature biotechnology

    2017  Volume 35, Issue 12, Page(s) 1145–1146

    Language English
    Publishing date 2017-11-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1311932-1
    ISSN 1546-1696 ; 1087-0156
    ISSN (online) 1546-1696
    ISSN 1087-0156
    DOI 10.1038/nbt.4009
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  2. Article ; Online: Repertoire-scale determination of class II MHC peptide binding via yeast display improves antigen prediction.

    Rappazzo, C Garrett / Huisman, Brooke D / Birnbaum, Michael E

    Nature communications

    2020  Volume 11, Issue 1, Page(s) 4414

    Abstract: ... ...

    Abstract CD4
    MeSH term(s) Binding Sites ; CD4-Positive T-Lymphocytes/immunology ; Cell Surface Display Techniques ; Databases, Protein ; Epitopes, T-Lymphocyte/chemistry ; Epitopes, T-Lymphocyte/genetics ; Epitopes, T-Lymphocyte/metabolism ; Genes, MHC Class II ; Histocompatibility Antigens Class II/metabolism ; Humans ; Oligopeptides/chemistry ; Oligopeptides/genetics ; Oligopeptides/metabolism ; Protein Binding/genetics ; Receptors, Antigen, T-Cell ; Recombinant Proteins/metabolism ; Saccharomyces cerevisiae/metabolism
    Chemical Substances Epitopes, T-Lymphocyte ; Histocompatibility Antigens Class II ; MHC binding peptide ; Oligopeptides ; Receptors, Antigen, T-Cell ; Recombinant Proteins
    Language English
    Publishing date 2020-09-04
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-020-18204-2
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  3. Article ; Online: Defining and Studying B Cell Receptor and TCR Interactions.

    Rappazzo, C Garrett / Fernández-Quintero, Monica L / Mayer, Andreas / Wu, Nicholas C / Greiff, Victor / Guthmiller, Jenna J

    Journal of immunology (Baltimore, Md. : 1950)

    2023  Volume 211, Issue 3, Page(s) 311–322

    Abstract: BCRs (Abs) and TCRs (or adaptive immune receptors [AIRs]) are the means by which the adaptive immune system recognizes foreign and self-antigens, playing an integral part in host defense, as well as the emergence of autoimmunity. Importantly, the ... ...

    Abstract BCRs (Abs) and TCRs (or adaptive immune receptors [AIRs]) are the means by which the adaptive immune system recognizes foreign and self-antigens, playing an integral part in host defense, as well as the emergence of autoimmunity. Importantly, the interaction between AIRs and their cognate Ags defies a simple key-in-lock paradigm and is instead a complex many-to-many mapping between an individual's massively diverse AIR repertoire, and a similarly diverse antigenic space. Understanding how adaptive immunity balances specificity with epitopic coverage is a key challenge for the field, and terms such as broad specificity, cross-reactivity, and polyreactivity remain ill-defined and are used inconsistently. In this Immunology Notes and Resources article, a group of experimental, structural, and computational immunologists define commonly used terms associated with AIR binding, describe methodologies to study these binding modes, as well as highlight the implications of these different binding modes for therapeutic design.
    MeSH term(s) Antigens ; Receptors, Antigen, T-Cell ; Receptors, Antigen, B-Cell ; Immune System/metabolism ; Autoimmunity
    Chemical Substances Antigens ; Receptors, Antigen, T-Cell ; Receptors, Antigen, B-Cell
    Language English
    Publishing date 2023-07-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.2300136
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  4. Article: Characteristics and functions of infection-enhancing antibodies to the N-terminal domain of SARS-CoV-2.

    Connor, Ruth I / Sakharkar, Mrunal / Rappazzo, C Garrett / Kaku, Chengzi I / Curtis, Nicholas C / Shin, Seungmin / Wieland-Alter, Wendy F / Weiner, Joshua A / Ackerman, Margaret E / Walker, Laura M / Lee, Jiwon / Wright, Peter F

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Characterization of functional antibody responses to the N-terminal domain (NTD) of the SARS-CoV-2 spike (S) protein has included identification of both potent neutralizing activity and putative enhancement of infection. Fcγ-receptor (FcγR)-independent ... ...

    Abstract Characterization of functional antibody responses to the N-terminal domain (NTD) of the SARS-CoV-2 spike (S) protein has included identification of both potent neutralizing activity and putative enhancement of infection. Fcγ-receptor (FcγR)-independent enhancement of SARS-CoV-2 infection mediated by NTD-binding monoclonal antibodies (mAbs) has been observed
    Language English
    Publishing date 2023-09-20
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.09.19.558444
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Repertoire-scale determination of class II MHC peptide binding via yeast display improves antigen prediction

    C. Garrett Rappazzo / Brooke D. Huisman / Michael E. Birnbaum

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 14

    Abstract: Identifying peptides that can bind major histocompatibility complex II (MHC-II) is important for our understanding of T cell immunity and specificity. Here the authors present a yeast-display library screening approach that identifies more potential ... ...

    Abstract Identifying peptides that can bind major histocompatibility complex II (MHC-II) is important for our understanding of T cell immunity and specificity. Here the authors present a yeast-display library screening approach that identifies more potential binders than various reported algorithms to help expand our understanding for antigen presentation.
    Keywords Science ; Q
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Repertoire-scale determination of class II MHC peptide binding via yeast display improves antigen prediction

    C. Garrett Rappazzo / Brooke D. Huisman / Michael E. Birnbaum

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 14

    Abstract: Identifying peptides that can bind major histocompatibility complex II (MHC-II) is important for our understanding of T cell immunity and specificity. Here the authors present a yeast-display library screening approach that identifies more potential ... ...

    Abstract Identifying peptides that can bind major histocompatibility complex II (MHC-II) is important for our understanding of T cell immunity and specificity. Here the authors present a yeast-display library screening approach that identifies more potential binders than various reported algorithms to help expand our understanding for antigen presentation.
    Keywords Science ; Q
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Potently neutralizing and protective anti-human metapneumovirus antibodies target diverse sites on the fusion glycoprotein.

    Rappazzo, C Garrett / Hsieh, Ching-Lin / Rush, Scott A / Esterman, Emma S / Delgado, Teresa / Geoghegan, James C / Wec, Anna Z / Sakharkar, Mrunal / Más, Vicente / McLellan, Jason S / Walker, Laura M

    Immunity

    2022  Volume 55, Issue 9, Page(s) 1710–1724.e8

    Abstract: Human metapneumovirus (hMPV) is a leading cause of acute lower respiratory tract infections in high-risk populations, yet there are no vaccines or anti-viral therapies approved for the prevention or treatment of hMPV-associated disease. Here, we used a ... ...

    Abstract Human metapneumovirus (hMPV) is a leading cause of acute lower respiratory tract infections in high-risk populations, yet there are no vaccines or anti-viral therapies approved for the prevention or treatment of hMPV-associated disease. Here, we used a high-throughput single-cell technology to interrogate memory B cell responses to the hMPV fusion (F) glycoprotein in young adult and elderly donors. Across all donors, the neutralizing antibody response was primarily directed to epitopes expressed on both pre- and post-fusion F conformations. However, we identified rare, highly potent broadly neutralizing antibodies that recognize pre-fusion-specific epitopes and structurally characterized an antibody that targets a site of vulnerability at the pre-fusion F trimer apex. Additionally, monotherapy with neutralizing antibodies targeting three distinct antigenic sites provided robust protection against lower respiratory tract infection in a small animal model. This study provides promising monoclonal antibody candidates for passive immunoprophylaxis and informs the rational design of hMPV vaccine immunogens.
    MeSH term(s) Aged ; Animals ; Antibodies, Neutralizing ; Antibodies, Viral ; Epitopes ; Glycoproteins ; Humans ; Metapneumovirus ; Respiratory Tract Infections ; Viral Fusion Proteins ; Young Adult
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral ; Epitopes ; Glycoproteins ; Viral Fusion Proteins
    Language English
    Publishing date 2022-08-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2022.07.003
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    Zs.A 4227: Show issues Location:
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  8. Article ; Online: Characteristics and functions of infection-enhancing antibodies to the N-terminal domain of SARS-CoV-2

    Connor, Ruth I. / Sakharkar, Mrunal / Rappazzo, C. Garrett / Kaku, Chengzi I. / Curtis, Nicholas C. / Shin, Seungmin / Wieland-Alter, Wendy F. / Weiner, Joshua A. / Ackerman, Margaret E. / Walker, Laura M. / Lee, Jiwon / Wright, Peter F.

    bioRxiv

    Abstract: Characterization of functional antibody responses to the N-terminal domain (NTD) of the SARS-CoV-2 spike (S) protein has included identification of both potent neutralizing activity and putative enhancement of infection. Fcγ-receptor (FcγR)-independent ... ...

    Abstract Characterization of functional antibody responses to the N-terminal domain (NTD) of the SARS-CoV-2 spike (S) protein has included identification of both potent neutralizing activity and putative enhancement of infection. Fcγ-receptor (FcγR)-independent enhancement of SARS-CoV-2 infection mediated by NTD-binding monoclonal antibodies (mAbs) has been observed in vitro, but the functional significance of these antibodies in vivo is not clear. Here we studied 1,213 S-binding mAbs derived from longitudinal sampling of B-cells collected from eight COVID-19 convalescent patients and identified 72 (5.9%) mAbs that enhanced infection in a VSV-SARS-CoV-2-S-Wuhan pseudovirus (PV) assay. The majority (68%) of these mAbs recognized the NTD, were identified in patients with mild and severe disease, and persisted for at least five months post-infection. Enhancement of PV infection by NTD-binding mAbs was not observed using intestinal (Caco-2) and respiratory (Calu-3) epithelial cells as infection targets and was diminished or lost against SARS-CoV-2 variants of concern (VOC). Proteomic deconvolution of the serum antibody repertoire from two of the convalescent subjects identified, for the first time, NTD-binding, infection-enhancing mAbs among the circulating immunoglobulins directly isolated from serum (i.e., functionally secreted antibody). Functional analysis of these mAbs demonstrated robust activation of FcγRIIIa associated with antibody binding to recombinant S proteins. Taken together, these findings suggest functionally active NTD-specific mAbs arise frequently during natural infection and can last as major serum clonotypes during convalescence. These antibodies display diverse attributes that include FcγR activation, and may be selected against by mutations in NTD associated with SARS-CoV-2 VOC.
    Keywords covid19
    Language English
    Publishing date 2023-09-20
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2023.09.19.558444
    Database COVID19

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  9. Article ; Online: Vaccination reshapes the virus-specific T cell repertoire in unexposed adults.

    Pan, Yi-Gen / Aiamkitsumrit, Benjamas / Bartolo, Laurent / Wang, Yifeng / Lavery, Criswell / Marc, Adam / Holec, Patrick V / Rappazzo, C Garrett / Eilola, Theresa / Gimotty, Phyllis A / Hensley, Scott E / Antia, Rustom / Zarnitsyna, Veronika I / Birnbaum, Michael E / Su, Laura F

    Immunity

    2021  Volume 54, Issue 6, Page(s) 1245–1256.e5

    Abstract: We examined how baseline ... ...

    Abstract We examined how baseline CD4
    MeSH term(s) Adult ; Animals ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Antigens, Viral/immunology ; CD4-Positive T-Lymphocytes/immunology ; Cells, Cultured ; Chlorocebus aethiops ; Humans ; Receptors, Antigen, T-Cell/immunology ; Vaccination/methods ; Vero Cells ; Yellow Fever/immunology ; Yellow Fever/virology ; Yellow Fever Vaccine/immunology ; Yellow fever virus/immunology
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral ; Antigens, Viral ; Receptors, Antigen, T-Cell ; Yellow Fever Vaccine
    Language English
    Publishing date 2021-05-18
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2021.04.023
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  10. Article ; Online: Viral immunity: Basic mechanisms and therapeutic applications-a Keystone Symposia report.

    Cable, Jennifer / Balachandran, Siddharth / Daley-Bauer, Lisa P / Rustagi, Arjun / Antony, Ferrin / Frere, Justin J / Strampe, Jamie / Kedzierska, Katherine / Cannon, Judy L / McGargill, Maureen A / Weiskopf, Daniela / Mettelman, Robert C / Niessl, Julia / Thomas, Paul G / Briney, Bryan / Valkenburg, Sophie A / Bloom, Jesse D / Bjorkman, Pamela J / Iketani, Sho /
    Rappazzo, C Garrett / Crooks, Chelsea M / Crofts, Kali F / Pöhlmann, Stefan / Krammer, Florian / Sant, Andrea J / Nabel, Gary J / Schultz-Cherry, Stacey

    Annals of the New York Academy of Sciences

    2023  Volume 1521, Issue 1, Page(s) 32–45

    Abstract: Viruses infect millions of people each year. Both endemic viruses circulating throughout the population as well as novel epidemic and pandemic viruses pose ongoing threats to global public health. Developing more effective tools to address viruses ... ...

    Abstract Viruses infect millions of people each year. Both endemic viruses circulating throughout the population as well as novel epidemic and pandemic viruses pose ongoing threats to global public health. Developing more effective tools to address viruses requires not only in-depth knowledge of the virus itself but also of our immune system's response to infection. On June 29 to July 2, 2022, researchers met for the Keystone symposium "Viral Immunity: Basic Mechanisms and Therapeutic Applications." This report presents concise summaries from several of the symposium presenters.
    MeSH term(s) Humans ; Pandemics ; Influenza, Human/epidemiology
    Language English
    Publishing date 2023-01-30
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 211003-9
    ISSN 1749-6632 ; 0077-8923
    ISSN (online) 1749-6632
    ISSN 0077-8923
    DOI 10.1111/nyas.14960
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