HIV-1 envelope gp41 antibodies can originate from terminal ileum B cells that share cross-reactivity with commensal bacteria.
Abstract
Monoclonal antibodies derived from blood plasma cells of acute HIV-1-infected individuals
are predominantly targeted to the HIV Env gp41 and cross-reactive with commensal bacteria.
To understand this phenomenon, we examined anti-HIV responses in ileum B cells using
recombinant antibody technology and probed their relationship to commensal bacteria.
The dominant ileum B cell response was to Env gp41. Remarkably, a majority (82%) of
the ileum anti-gp41 antibodies cross-reacted with commensal bacteria, and of those,
43% showed non-HIV-1 antigen polyreactivity. Pyrosequencing revealed shared HIV-1
antibody clonal lineages between ileum and blood. Mutated immunoglobulin G antibodies
cross-reactive with both Env gp41 and microbiota could also be isolated from the ileum
of HIV-1 uninfected individuals. Thus, the gp41 commensal bacterial antigen cross-reactive
antibodies originate in the intestine, and the gp41 Env response in HIV-1 infection
can be derived from a preinfection memory B cell pool triggered by commensal bacteria
that cross-react with Env.
Type
Journal articleSubject
Antibody SpecificityAntigens, Bacterial
Cross Reactions
HIV Antibodies
HIV Envelope Protein gp41
HIV Infections
HIV-1
Humans
Ileum
Microbiota
Molecular Sequence Data
Plasma Cells
Protein Binding
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https://hdl.handle.net/10161/9021Published Version (Please cite this version)
10.1016/j.chom.2014.07.003Publication Info
(2014). HIV-1 envelope gp41 antibodies can originate from terminal ileum B cells that share
cross-reactivity with commensal bacteria. Cell Host Microbe, 16(2). pp. 215-226. 10.1016/j.chom.2014.07.003. Retrieved from https://hdl.handle.net/10161/9021.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
S. Munir Alam
Professor in Medicine
Research Interests.
The Alam laboratory’s primary research is focused on understanding the biophysical
properties of antigen-antibody binding and the molecular events of early B cell activation
using the HIV-1 broadly neutralizing antibody (bnAb) lineage models. We are studying
how HIV-1 Envelope proteins of varying affinities are sensed by B cells expressing
HIV-1 bnAbs or their germline antigen receptors and initiate early signaling events
for their activation. In the lon
Barton Ford Haynes
Frederic M. Hanes Distinguished Professor of Medicine
Barton F. Haynes, M.D. is the Frederic M. Hanes Professor of Medicine and Immunology,
and Director of the Duke Human Vaccine Institute. Prior to leading the DHVI, Dr. Haynes
served as Chief of the Division of Rheumatology, Allergy and Clinical Immunology,
and later as Chair of the Department of Medicine. As Director of the Duke Human Vaccine
Institute, Bart Haynes is leading a team of investigators working on vaccines for
emerging infections, including tuberculosis, pandemic influenza, emergi
Kwan-Ki Hwang
Research Scientist, Senior
Hua-Xin Liao
Adjunct Professor in the Department of Medicine
Dr. Liao is a Professor of Medicine and Research Director of Duke Human Vaccine Institute.
Dr. Liao is a MD virologistt rained in China. In early 1980’s, Dr. Liao made
major contributions to the first isolation of epidemic hemorrhagic fever virus (hataanvirus)
from Apodemus agraius using tissue culture in China. The successful identification
and isolation of Hataanvirus enabled the early diagnosis and treatment of the disease,
and advancement of HFRS research towards prevention by de
This author no longer has a Scholars@Duke profile, so the information shown here reflects
their Duke status at the time this item was deposited.
Michael Anthony Moody
Professor of Pediatrics
Tony Moody, MD is a Professor in the Department of Pediatrics, Division of Infectious
Diseases and Professor in the Department of Integrative Immunobiology at Duke University
Medical Center. Research in the Moody lab is focused on understanding the B cell responses
during infection, vaccination, and disease. The lab has become a resource for human
phenotyping, flow characterization, staining and analysis at the Duke Human Vaccine
Institute (DHVI). The Moody lab is currently funded to study in
Georgia Doris Tomaras
Professor in Surgery
Dr. Georgia Tomaras is a tenured Professor of Surgery, Professor of Immunology, Professor
of Molecular Genetics and Microbiology and is a Fellow of the American Academy of
Microbiology (AAM) and a Fellow of the American Association for the Advancement of
Science (AAAS). Dr. Tomaras is Co-Director of the Center for Human Systems Immunology
(CHSI) Duke University and Director of the Duke Center for AIDS Research (CFAR). Her
national and international leadership roles i
Nathan A. Vandergrift
Associate Professor in Medicine
John Franklin Whitesides
Assistant Professor in Medicine
Kevin J Wiehe
Norman L. Letvin Associate Professor in Medicine
Dr. Kevin Wiehe is the associate director of research, director of computational biology
and co-director of the Quantitative Research Division at the Duke Human Vaccine Institute
(DHVI). He has over 20 years of experience in the field of computational biology and
has expertise in computational structural biology, computational genomics, and computational
immunology.
For the past decade, he has applied his unique background to developing computational
approaches for studying the B cell
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