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High-Resolution Interrogation of Antibody Repertoires Using Next-Generation Sequencing

dc.contributor.advisorCrowe, James E
dc.creatorSetliff, Marion
dc.date.accessioned2020-09-22T21:33:06Z
dc.date.created2020-01
dc.date.issued2020-01-21
dc.date.submittedJanuary 2020
dc.identifier.urihttp://hdl.handle.net/1803/16000
dc.description.abstractPathogen-specific human B cells represent a rich source of antibodies that have been selected for by the process of affinity maturation. In the last few decades, a number of approaches have been developed for the identification and isolation of human monoclonal antibodies with desired characteristics. These methods suffer either from scalability constraints or an inability to perform parallel screens against multiple antigens or antigen variants. Here, we propose that recent advances in molecular genomics technologies can be applied to antibody discovery efforts to amplify throughput and parallelizability. We first use deep sequencing of the antibody heavy chain repertoire from pre-infection through chronic HIV infection in a cohort of HIV-infected subjects to characterize how the antibody repertoire evolves in response to infection. In so doing, we identified public HIV-specific antibodies shared by multiple donors, and characterized them functionally. We show that the use of next-generation sequencing technologies becomes especially useful upon converting antibody functional properties into sequencing-detectable events. We describe novel technologies that enable the coupling of antibody sequence and function and demonstrate their use in isolating broadly neutralizing HIV antibodies and broadly-reactive influenza antibodies.
dc.format.mimetypeapplication/pdf
dc.language.isoen
dc.subjectAntibody
dc.subjectAntibody Repertoire
dc.subjectImmunology
dc.subjectAntibody Discovery
dc.titleHigh-Resolution Interrogation of Antibody Repertoires Using Next-Generation Sequencing
dc.typeThesis
dc.date.updated2020-09-22T21:33:07Z
dc.contributor.committeeMemberOgden, Kristen
dc.contributor.committeeMemberMeilier, Jens
dc.contributor.committeeMemberKalams, Spyros
dc.type.materialtext
thesis.degree.namePhD
thesis.degree.levelDoctoral
thesis.degree.disciplineChemical & Physical Biology
thesis.degree.grantorVanderbilt University Graduate School
local.embargo.terms2022-01-01
local.embargo.lift2022-01-01
dc.creator.orcid0000-0003-4726-6132


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