High-throughput methods for characterizing the immune repertoire

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.

Department dc:contributor.department

Harvard--MIT Program in Health Sciences and Technology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2013

Author dc:creator

• Laserson, Uri

Advisor dc:contributor.advisor

• George M Church.

• Harvard--MIT Program in Health Sciences and Technology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/79246

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/79246