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High-throughput methods for characterizing the immune repertoire

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Author(s)
Laserson, Uri
Advisor(s)
George M Church.
Date Issued
2013
Publisher
Massachusetts Institute of Technology
Abstract
The adaptive immune system is one of the primary mediators in almost every major human disease, including infections, cancer, autoimmunity, and inflammation-based disorders. It fundamentally functions as a molecular classifier, and stores a memory of its previous exposures. However, until recently, methods to unlock this information or to exploit its power in the form of new therapeutic antibodies or affinity reagents have been limited by the use of traditional, low-throughput technologies. In this thesis, we leverage recent advances in high-throughput DNA sequencing technology to develop new methods to characterize and probe the immune repertoire in unprecedented detail. We use this technology to 1) characterize the rapid dynamics of the immune repertoire in response to influenza vaccination, 2) characterize elite neutralizing antibodies to HIV, to better understand the constraints for designing an HIV vaccine, and 3) develop new methodologies for discovering auto-antigens, and assaying large libraries of protein antigens in general. We hope that these projects will serve as stepping-stones towards filling the gap left by low-throughput methods in the development of antibody technologies.
Description
Thesis (Ph. D. in Biomedical Engineering and Computational Biology)--Harvard-MIT Program in Health Sciences and Technology, February 2013.
"September 2012." Cataloged from PDF version of thesis.
Includes bibliographical references (p. 147-160).
Subjects
Harvard--MIT Program in Health Sciences and Technology.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
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