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HIV-1 envelope gp41 antibodies can originate from terminal ileum B cells that share cross-reactivity with commensal bacteria.

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Date
2014-08-13
Authors
Trama, A
Moody, MA
Alam, SM
Jaeger, F
Lockwood, B
Parks, R
Lloyd, K
Stolarchuk, C
Scearce, R
Foulger, A
Marshall, D
Whitesides, J
Jeffries, T
Wiehe, K
Morris, L
Lambson, B
Soderberg, K
Hwang, K
Tomaras, G
Vandergrift, N
Jackson, KL
Roskin, K
Boyd, S
Kepler, T
Liao, H
Haynes, B
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(26 total)
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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 article
Subject
Antibody Specificity
Antigens, Bacterial
Cross Reactions
HIV Antibodies
HIV Envelope Protein gp41
HIV Infections
HIV-1
Humans
Ileum
Microbiota
Molecular Sequence Data
Plasma Cells
Protein Binding
Permalink
https://hdl.handle.net/10161/9021
Published Version (Please cite this version)
10.1016/j.chom.2014.07.003
Publication Info
Trama, A; Moody, MA; Alam, SM; Jaeger, F; Lockwood, B; Parks, R; ... Haynes, B (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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Scholars@Duke

Alam

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
Haynes

Barton Ford Haynes

Frederic M. Hanes Distinguished 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

Kwan-Ki Hwang

Research Scientist, Senior
Liao

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
Moody

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 Immunology 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 influenza, syphil
Tomaras

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 the Director of the Duke Center for AIDS Research, a founding Director of the Duke Center for Human Systems Immunology, the Director of Lab Science and mPI for the HIV Vaccine Trials Ne
Vandergrift

Nathan A. Vandergrift

Associate Professor in Medicine

John Franklin Whitesides

Assistant Professor in Medicine
Wiehe

Kevin J Wiehe

Associate Professor in Medicine
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