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Staphylococcal phosphatidylglycerol antigens activate human T cells via CD1a

Monnot, Gwennaëlle C., Wegrecki, Marcin, Cheng, Tan-Yun, Chen, Yi-Ling, Sallee, Brigitte N., Chakravarthy, Reka, Karantza, Ioanna Maria, Tin, Shin Yi, Khaleel, Alexandra E., Monga, Isha, Uwakwe, Laura N., Tillman, Alice, Cheng, Bin, Youssef, Soundos, Ng, Soo Weei, Shahine, Adam, Garcia-Vilas, Javier A., Uhlemann, Anne-Catrin, Bordone, Lindsey A., Han, Arnold, Rohde, Christine H., Ogg, Graham, Moody, D. Branch, Rossjohn, Jamie ORCID: and de Jong, Annemieke 2023. Staphylococcal phosphatidylglycerol antigens activate human T cells via CD1a. Nature Immunology 24 (1) , pp. 110-122. 10.1038/s41590-022-01375-z

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Expressed on epidermal Langerhans cells, CD1a presents a range of self-lipid antigens found within the skin; however, the extent to which CD1a presents microbial ligands from bacteria colonizing the skin is unclear. Here we identified CD1a-dependent T cell responses to phosphatidylglycerol (PG), a ubiquitous bacterial membrane phospholipid, as well as to lysylPG, a modified PG, present in several Gram-positive bacteria and highly abundant in Staphylococcus aureus. The crystal structure of the CD1a–PG complex showed that the acyl chains were buried within the A′- and F′-pockets of CD1a, while the phosphoglycerol headgroup remained solvent exposed in the F′-portal and was available for T cell receptor contact. Using lysylPG and PG-loaded CD1a tetramers, we identified T cells in peripheral blood and in skin that respond to these lipids in a dose-dependent manner. Tetramer+CD4+ T cell lines secreted type 2 helper T cell cytokines in response to phosphatidylglycerols as well as to co-cultures of CD1a+ dendritic cells and Staphylococcus bacteria. The expansion in patients with atopic dermatitis of CD4+ CD1a–(lysyl)PG tetramer+ T cells suggests a response to lipids made by bacteria associated with atopic dermatitis and provides a link supporting involvement of PG-based lipid-activated T cells in atopic dermatitis pathogenesis.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Nature Research
ISSN: 1529-2908
Date of Acceptance: 31 October 2022
Last Modified: 11 Apr 2023 15:15

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