Watson, Avia, Li, Hao ORCID: 0000-0002-4131-5207, Ma, Bingting, Weiss, Ronen, Bendayan, Daniele, Abramovitz, Lilach, Ben-Shalom, Noam, Mor, Michael ORCID: 0000-0003-1361-4151, Pinko, Erica, Bar Oz, Michal ORCID: 0000-0002-1927-4592, Wang, Zhenqi, Du, Fengjiao, Lu, Yu, Rybniker, Jan, Dahan, Rony ORCID: 0000-0002-8420-7601, Huang, Hairong, Barkan, Daniel, Xiang, Ye, Javid, Babak and Freund, Natalia T. (2021). Human antibodies targeting a Mycobacterium transporter protein mediate protection against tuberculosis. Nat. Commun., 12 (1). BERLIN: NATURE PORTFOLIO. ISSN 2041-1723

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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 angstrom and 2.4 angstrom 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. Antibody responses against Mycobacteria infection have been reported, but whether and how they impact anti-bacteria immunity in the host is unclear. Here the authors characterize human anti-Mycobacteria antibodies to find them targeting a Mycobacteria transporter protein, PstS1, show distinct interaction modes in crystal structure, and mediate protection in vitro.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Watson, AviaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Li, HaoUNSPECIFIEDorcid.org/0000-0002-4131-5207UNSPECIFIED
Ma, BingtingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weiss, RonenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bendayan, DanieleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abramovitz, LilachUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ben-Shalom, NoamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mor, MichaelUNSPECIFIEDorcid.org/0000-0003-1361-4151UNSPECIFIED
Pinko, EricaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bar Oz, MichalUNSPECIFIEDorcid.org/0000-0002-1927-4592UNSPECIFIED
Wang, ZhenqiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Du, FengjiaoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lu, YuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rybniker, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dahan, RonyUNSPECIFIEDorcid.org/0000-0002-8420-7601UNSPECIFIED
Huang, HairongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barkan, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Xiang, YeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Javid, BabakUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Freund, Natalia T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-600822
DOI: 10.1038/s41467-021-20930-0
Journal or Publication Title: Nat. Commun.
Volume: 12
Number: 1
Date: 2021
Publisher: NATURE PORTFOLIO
Place of Publication: BERLIN
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CELLS; EXPRESSION; INFECTION; IMMUNITY; PSTS1; GAMMA; PCR; TBMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60082

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