Synthetic mycobacterial diacyl trehaloses reveal differential recognition by human T cell receptors and the C-type lectin Mincle

Abstract The cell wall of Mycobacterium tuberculosis is composed of diverse glycolipids which potentially interact with the human immune system. To overcome difficulties in obtaining pure compounds from bacterial extracts, we recently synthesized three forms of mycobacterial diacyltrehalose (DAT) th...

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Autores principales:	Josephine F. Reijneveld, Mira Holzheimer, David C. Young, Kattya Lopez, Sara Suliman, Judith Jimenez, Roger Calderon, Leonid Lecca, Megan B. Murray, Eri Ishikawa, Sho Yamasaki, Adriaan J. Minnaard, D. Branch Moody, Ildiko Van Rhijn
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/90220270f20747fdaf524d58aa1ac4a7
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spelling	oai:doaj.org-article:90220270f20747fdaf524d58aa1ac4a72021-12-02T13:57:05ZSynthetic mycobacterial diacyl trehaloses reveal differential recognition by human T cell receptors and the C-type lectin Mincle10.1038/s41598-021-81474-32045-2322https://doaj.org/article/90220270f20747fdaf524d58aa1ac4a72021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81474-3https://doaj.org/toc/2045-2322Abstract The cell wall of Mycobacterium tuberculosis is composed of diverse glycolipids which potentially interact with the human immune system. To overcome difficulties in obtaining pure compounds from bacterial extracts, we recently synthesized three forms of mycobacterial diacyltrehalose (DAT) that differ in their fatty acid composition, DAT1, DAT2, and DAT3. To study the potential recognition of DATs by human T cells, we treated the lipid-binding antigen presenting molecule CD1b with synthetic DATs and looked for T cells that bound the complex. DAT1- and DAT2-treated CD1b tetramers were recognized by T cells, but DAT3-treated CD1b tetramers were not. A T cell line derived using CD1b-DAT2 tetramers showed that there is no cross-reactivity between DATs in an IFN-γ release assay, suggesting that the chemical structure of the fatty acid at the 3-position determines recognition by T cells. In contrast with the lack of recognition of DAT3 by human T cells, DAT3, but not DAT1 or DAT2, activates Mincle. Thus, we show that the mycobacterial lipid DAT can be both an antigen for T cells and an agonist for the innate Mincle receptor, and that small chemical differences determine recognition by different parts of the immune system.Josephine F. ReijneveldMira HolzheimerDavid C. YoungKattya LopezSara SulimanJudith JimenezRoger CalderonLeonid LeccaMegan B. MurrayEri IshikawaSho YamasakiAdriaan J. MinnaardD. Branch MoodyIldiko Van RhijnNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Josephine F. Reijneveld Mira Holzheimer David C. Young Kattya Lopez Sara Suliman Judith Jimenez Roger Calderon Leonid Lecca Megan B. Murray Eri Ishikawa Sho Yamasaki Adriaan J. Minnaard D. Branch Moody Ildiko Van Rhijn Synthetic mycobacterial diacyl trehaloses reveal differential recognition by human T cell receptors and the C-type lectin Mincle
description	Abstract The cell wall of Mycobacterium tuberculosis is composed of diverse glycolipids which potentially interact with the human immune system. To overcome difficulties in obtaining pure compounds from bacterial extracts, we recently synthesized three forms of mycobacterial diacyltrehalose (DAT) that differ in their fatty acid composition, DAT1, DAT2, and DAT3. To study the potential recognition of DATs by human T cells, we treated the lipid-binding antigen presenting molecule CD1b with synthetic DATs and looked for T cells that bound the complex. DAT1- and DAT2-treated CD1b tetramers were recognized by T cells, but DAT3-treated CD1b tetramers were not. A T cell line derived using CD1b-DAT2 tetramers showed that there is no cross-reactivity between DATs in an IFN-γ release assay, suggesting that the chemical structure of the fatty acid at the 3-position determines recognition by T cells. In contrast with the lack of recognition of DAT3 by human T cells, DAT3, but not DAT1 or DAT2, activates Mincle. Thus, we show that the mycobacterial lipid DAT can be both an antigen for T cells and an agonist for the innate Mincle receptor, and that small chemical differences determine recognition by different parts of the immune system.
format	article
author	Josephine F. Reijneveld Mira Holzheimer David C. Young Kattya Lopez Sara Suliman Judith Jimenez Roger Calderon Leonid Lecca Megan B. Murray Eri Ishikawa Sho Yamasaki Adriaan J. Minnaard D. Branch Moody Ildiko Van Rhijn
author_facet	Josephine F. Reijneveld Mira Holzheimer David C. Young Kattya Lopez Sara Suliman Judith Jimenez Roger Calderon Leonid Lecca Megan B. Murray Eri Ishikawa Sho Yamasaki Adriaan J. Minnaard D. Branch Moody Ildiko Van Rhijn
author_sort	Josephine F. Reijneveld
title	Synthetic mycobacterial diacyl trehaloses reveal differential recognition by human T cell receptors and the C-type lectin Mincle
title_short	Synthetic mycobacterial diacyl trehaloses reveal differential recognition by human T cell receptors and the C-type lectin Mincle
title_full	Synthetic mycobacterial diacyl trehaloses reveal differential recognition by human T cell receptors and the C-type lectin Mincle
title_fullStr	Synthetic mycobacterial diacyl trehaloses reveal differential recognition by human T cell receptors and the C-type lectin Mincle
title_full_unstemmed	Synthetic mycobacterial diacyl trehaloses reveal differential recognition by human T cell receptors and the C-type lectin Mincle
title_sort	synthetic mycobacterial diacyl trehaloses reveal differential recognition by human t cell receptors and the c-type lectin mincle
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/90220270f20747fdaf524d58aa1ac4a7
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Synthetic mycobacterial diacyl trehaloses reveal differential recognition by human T cell receptors and the C-type lectin Mincle

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