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

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

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Article number2010
Pages (from-to)1-10
Number of pages10
JournalScientific Reports
Volume11
Issue number1
DOIs
Publication statusPublished - Dec 2021

Bibliographical note

Funding Information:
DBM was supported by National Institutes of Health (NIH) grant R01 AI049313. DBM, MM, and IVR were supported by and NIH Tuberculosis Research Unit Network, Grant U19 AI111224. JFR, MH, and AJM were supported by Nederlands Wetenschappelijk Onderzoek (NWO) Toppunt grant 15.002.

Publisher Copyright:
© 2021, The Author(s).

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