title: 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.
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA; Department of Immunology, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA. Electronic address: ashley.trama@dm.duke.edu.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Trama
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA; Department of Pediatrics, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA.
authors.forename: M Anthony
authors.initials: MA
authors.lastname: Moody
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA.
authors.forename: S Munir
authors.initials: SM
authors.lastname: Alam
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA.
authors.forename: Frederick H
authors.initials: FH
authors.lastname: Jaeger
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA.
authors.forename: Bradley
authors.initials: B
authors.lastname: Lockwood
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Parks
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA.
authors.forename: Krissey E
authors.initials: KE
authors.lastname: Lloyd
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Stolarchuk
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Scearce
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Foulger
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA.
authors.forename: Dawn J
authors.initials: DJ
authors.lastname: Marshall
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Whitesides
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Jeffries
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Wiehe
authors.affiliation: Centre for HIV and STIs, National Institute for Communicable Diseases, Johannesburg 2131, South Africa.
authors.forename: Lynn
authors.initials: L
authors.lastname: Morris
authors.affiliation: Centre for HIV and STIs, National Institute for Communicable Diseases, Johannesburg 2131, South Africa.
authors.forename: Bronwen
authors.initials: B
authors.lastname: Lambson
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Soderberg
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA.
authors.forename: Kwan-Ki
authors.initials: KK
authors.lastname: Hwang
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA; Department of Surgery, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA; Department of Molecular Genetics and Microbiology, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA.
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Vandergrift
authors.affiliation: Department of Pathology, Stanford University, Palo Alto, CA 94305, USA.
authors.forename: Katherine J L
authors.initials: KJL
authors.lastname: Jackson
authors.affiliation: Department of Pathology, Stanford University, Palo Alto, CA 94305, USA.
authors.forename: Krishna M
authors.initials: KM
authors.lastname: Roskin
authors.affiliation: Department of Pathology, Stanford University, Palo Alto, CA 94305, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Boyd
authors.affiliation: Department of Microbiology, Boston University, Boston, MA 02215, USA.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Kepler
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA.
authors.forename: Hua-Xin
authors.initials: HX
authors.lastname: Liao
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA; Department of Immunology, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine and Duke Global Health Institute, Durham, NC 27710, USA. Electronic address: barton.haynes@dm.duke.edu.
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
mesh_terms: D000918:Antibody Specificity; D000942:Antigens, Bacterial / Q000276:immunology; D003429:Cross Reactions; D015483:HIV Antibodies / Q000378:metabolism*; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007082:Ileum / Q000276:immunology* / Q000473:pathology / Q000821:virology; D064307:Microbiota / Q000276:immunology*; D008969:Molecular Sequence Data; D010950:Plasma Cells / Q000276:immunology / Q000821:virology; D011485:Protein Binding
chemical_list: D000942:Antigens, Bacterial; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; C514787:gp41 protein, Human immunodeficiency virus 1