Abstract |
Mycobacterium tuberculosis (Mtb) exposure drives antibody responses, but whether patients with active tuberculosis elicit protective antibodies, and against which antigens, is still unclear. Here we generate monoclonal antibodies from memory B cells of one patient to investigate the B cell responses during active infection. The antibodies, members of four distinct B cell clones, are directed against the Mtb phosphate transporter subunit PstS1. Antibodies p4-36 and p4-163 reduce Mycobacterium bovis-BCG and Mtb levels in an ex vivo human whole blood growth inhibition assay in an FcR-dependent manner; meanwhile, germline versions of p4-36 and p4-163 do not bind Mtb. Crystal structures of p4-36 and p4-170, complexed to PstS1, are determined at 2.1 Å and 2.4 Å resolution, respectively, to reveal two distinctive PstS1 epitopes. Lastly, a prophylactic p4-36 and p4-163 treatment in Mtb-infected Balb/c mice reduces bacterial lung burden by 50%. Our study shows that inhibitory anti-PstS1 B cell responses arise during active tuberculosis.
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Authors | Avia Watson, Hao Li, Bingting Ma, Ronen Weiss, Daniele Bendayan, Lilach Abramovitz, Noam Ben-Shalom, Michael Mor, Erica Pinko, Michal Bar Oz, Zhenqi Wang, Fengjiao Du, Yu Lu, Jan Rybniker, Rony Dahan, Hairong Huang, Daniel Barkan, Ye Xiang, Babak Javid, Natalia T Freund |
Journal | Nature communications
(Nat Commun)
Vol. 12
Issue 1
Pg. 602
(01 27 2021)
ISSN: 2041-1723 [Electronic] England |
PMID | 33504803
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Bacterial
- Antibodies, Monoclonal
- Bacterial Proteins
- Epitopes
- Membrane Transport Proteins
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Topics |
- Adult
- Amino Acid Sequence
- Animals
- Antibodies, Bacterial
(immunology)
- Antibodies, Monoclonal
(immunology, isolation & purification)
- B-Lymphocytes
(immunology)
- Bacterial Proteins
(chemistry, immunology)
- Epitopes
(chemistry)
- Humans
- Immunologic Memory
- Male
- Membrane Transport Proteins
(immunology)
- Mice, Inbred BALB C
- Models, Molecular
- Mycobacterium tuberculosis
(immunology)
- Protein Structure, Secondary
- Structure-Activity Relationship
- THP-1 Cells
- Tuberculosis
(blood, immunology, microbiology, prevention & control)
- Mice
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