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Structural Characterizations of the Dimeric Anti-HIV Antibody 2G12 and the HIV-2 Envelope Glycoprotein


Wu, Yunji (2015) Structural Characterizations of the Dimeric Anti-HIV Antibody 2G12 and the HIV-2 Envelope Glycoprotein. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z98050K6.


More than thirty years after the discovery that Human Immunodeficiency Virus (HIV) was the causative agent of Acquired Immunodeficiency Syndrome (AIDS), the disease remains pandemic as long as no effective universal vaccine is found. Over 34 million individuals in the world are infected with the virus, and the vast majority of them have no access to the antiretroviral therapies that have largely reduced HIV to a chronic disease in the developed world. The first chapter of this thesis introduces the history of the virus. The key to the infectious mechanism of the virus lies in its envelope glycoprotein (Env), a trimeric spike on the viral surface that utilizes host T cell receptors for entry. Though HIV-1 Env is immunogenic, most infected patients do not mount an effective neutralizing antibody response against it. Broadly-neutralizing anti-Env antibodies (bNAbs) present in the serum of a minority of infected individuals are usually sufficient to prevent the progression to full blown AIDS. Thus, the molecular details of these bNAbs as well as the antibody-antigen interface are of prime interest for structural studies, as insight gained would contribute to the design of a more effective immunogen and potential vaccine candidate. The second chapter of this thesis describes the low-resolution crystal structure of one such antibody, 2G12 dimer, which targets a high mannose epitope on the surface of Env. Patients infected with HIV-2, a related virus with ~35% sequence identity in the Env region, can generally mount a robust antibody response sufficient for viral control for reasons still unknown. The final two chapters of this thesis focus on the first reported structural studies of HIV-2 Env, the molecular details of which may inform HIV-1 therapy and immunogen design.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:HIV, antibodies, X-ray crystallography, single particle electron microscopy
Degree Grantor:California Institute of Technology
Division:Biology and Biological Engineering
Major Option:Molecular Biology and Biochemistry
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Bjorkman, Pamela J.
Thesis Committee:
  • Chan, David C. (chair)
  • Baltimore, David L.
  • Rees, Douglas C.
  • Bjorkman, Pamela J.
Defense Date:29 April 2015
Funding AgencyGrant Number
NIH2 R37AI041239-06A1
NIH 5 T32 GM 7616-33
Bill and Melinda Gates FoundationCAVD
Record Number:CaltechTHESIS:05212015-194407438
Persistent URL:
Related URLs:
URLURL TypeDescription CentralArticle adapted for Chapter 2
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:8878
Deposited By: Yunji Wu
Deposited On:26 May 2015 21:20
Last Modified:08 Nov 2023 00:16

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