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

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

United States

2014-08-13T16:50:56Z

2014-08-13

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.

http://www.ncbi.nlm.nih.gov/pubmed/25121750

S1931-3128(14)00257-1

1934-6069

https://hdl.handle.net/10161/9021

eng

Elsevier

Cell Host Microbe

10.1016/j.chom.2014.07.003

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

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

Journal article

Moody, MA|0000-0002-3890-5855

Alam, SM|0000-0003-0941-0703

Tomaras, G|0000-0001-8076-1931

http://www.ncbi.nlm.nih.gov/pubmed/25121750

215

226

2

Basic Science Departments

Clinical Science Departments

Duke

Duke Cancer Institute

Duke Human Vaccine Institute

Global Health Institute

Immunology

Institutes and Centers

Institutes and Provost's Academic Units

Medicine

Medicine, Duke Human Vaccine Institute

Molecular Genetics and Microbiology

Pathology

Pediatrics

Pediatrics, Infectious Diseases

School of Medicine

Surgery

Surgery, Surgical Sciences

University Institutes and Centers

Published

16