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 Professor of Medicine
The Haynes lab is studying host innate and adaptive immune responses to the human
immunodeficiency virus (HIV), tuberculosis (TB), and influenza in order to find the
enabling technology to make preventive vaccines against these three major infectious
diseases. Mucosal Immune Responses in Acute HIV Infection The Haynes lab is working
to determine why broadly neutralizing antibodies are rarely made in acute HIV infection
(AHI), currently a major obstacle in the de
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
Georgia Doris Tomaras
Professor in Surgery
Research in the Tomaras Laboratory in the Duke Human Vaccine Institute and Departments
of Surgery, Immunology, and Molecular Genetics and Microbiology at Duke University
Medical Center, focuses on the identification of immune correlates of protection for
preventative vaccines and identification of the mechanisms responsible for potent
inhibition of human pathogens.
Nathan A. Vandergrift
Associate Professor in Medicine
John Franklin Whitesides
Assistant Professor in Medicine
Kevin J Wiehe
Assistant Professor in Medicine
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