Dataset Information

Next-generation Serology by Mass Spectrometry:Readout of the SARS-CoV-2 Antibody Repertoire

ABSTRACT: Methods of antibody detection are used to assess exposure or immunity to a pathogen. Here, we present Ig-MS, a novel serological readout that captures the immunoglobulin (Ig) repertoire at molecular resolution, including entire variable regions in Ig light and heavy chains. Ig-MS uses new advances in protein mass spectrometry (MS) for multi-parametric readout of antibodies, with new metrics like Ion Titer (IT) and degree of clonality (DoC) capturing the heterogeneity and relative abundance of individual clones without sequencing of B cells. We apply Ig-MS to plasma from subjects with severe & mild COVID-19, using the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 as the bait for antibody capture. Importantly, we report a new data type for human serology, with compatibility to any recombinant antigen to gauge our immune responses to vaccination, pathogens, or autoimmune disorders.

ORGANISM(S): Homo Sapiens

SUBMITTER: Young Ah Goo

PROVIDER: PXD028627 | panorama | Sat Sep 24 00:00:00 BST 2022

REPOSITORIES: PanoramaPublic

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Publications

Next-Generation Serology by Mass Spectrometry: Readout of the SARS-CoV-2 Antibody Repertoire.

Melani Rafael D RD Des Soye Benjamin J BJ Kafader Jared O JO Forte Eleonora E Hollas Michael M Blagojevic Voislav V Negrão Fernanda F McGee John P JP Drown Bryon B Lloyd-Jones Cameron C Seckler Henrique S HS Camarillo Jeannie M JM Compton Philip D PD LeDuc Richard D RD Early Bryan B Fellers Ryan T RT Cho Byoung-Kyu BK Mattamana Basil Baby BB Goo Young Ah YA Thomas Paul M PM Ash Michelle K MK Bhimalli Pavan P PP Al-Harthi Lena L Sha Beverly E BE Schneider Jeffrey R JR Kelleher Neil L NL

Journal of proteome research 20211208 1

Methods of antibody detection are used to assess exposure or immunity to a pathogen. Here, we present Ig-MS, a novel serological readout that captures the immunoglobulin (Ig) repertoire at molecular resolution, including entire variable regions in Ig light and heavy chains. Ig-MS uses recent advances in protein mass spectrometry (MS) for multiparametric readout of antibodies, with new metrics like Ion Titer (IT) and Degree of Clonality (DoC) capturing the heterogeneity and relative abundance of ...[more]

PMID: 34878788

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Project description:Throughout life, humans experience repeated exposure to viral antigens through infection and vaccination, resulting in the generation of diverse, and largely unique, antigen specific antibody repertoires. A paramount feature of antibodies that enables their critical contributions in counteracting recurrent and novel pathogens, and consequently fostering their utility as valuable targets for therapeutic and vaccine development, is the exquisite specificity displayed against their target antigens. Yet, there is still limited understanding of the determinants of antibody-antigen specificity, particularly as a function of antibody sequence. In recent years, experimental characterization of antibody repertoires has led to novel insights into fundamental properties of antibody sequences, but has been largely decoupled from at-scale antigen specificity analysis. Here, using the LIBRA-seq technology, we generated a large dataset mapping antibody sequence to antigen specificity for thousands of B cells, by screening the repertoires of a set of healthy individuals against twenty viral antigens representing diverse pathogens of biomedical significance. Analysis uncovered virus specific patterns in variable gene usage, gene pairing, somatic hypermutation, as well as the presence of convergent antiviral signatures across multiple individuals, including the presence of public antibody clonotypes. Notably, our results showed that, for B cell receptors originating from different individuals but leveraging an identical combination of heavy and light chain variable genes, there is a specific CDRH3/CDRL3 identity threshold that defines whether these B cells may share the same antigen specificity. This finding provides a quantifiable measure of the relationship between antibody sequence and antigen specificity and further defines experimentally grounded criteria for defining public antibody clonality. Understanding the fundamental rules of antibody-antigen interactions can lead to transformative new approaches for the development of antibody therapeutics and vaccines against current and emerging viruses.

Dataset Information

Next-generation Serology by Mass Spectrometry:Readout of the SARS-CoV-2 Antibody Repertoire

Publications

Next-Generation Serology by Mass Spectrometry: Readout of the SARS-CoV-2 Antibody Repertoire.

Similar Datasets

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