7SH4

CD1a-phosphatidylglycerol binary structure

Summary for 7SH4

• Entry DOI: 10.2210/pdb7sh4/pdb
• Descriptor: T-cell surface glycoprotein CD1a, Beta-2-microglobulin, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: cd1, antigen presentation, lipid, immune system, phospholipid
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 46554.40

Authors

Wegrecki, M.,Rossjohn, J. (deposition date: 2021-10-07, release date: 2022-10-05, Last modification date: 2024-10-16)

Primary citation

Monnot, G.C.,Wegrecki, M.,Cheng, T.Y.,Chen, Y.L.,Sallee, B.N.,Chakravarthy, R.,Karantza, I.M.,Tin, S.Y.,Khaleel, A.E.,Monga, I.,Uwakwe, L.N.,Tillman, A.,Cheng, B.,Youssef, S.,Ng, S.W.,Shahine, A.,Garcia-Vilas, J.A.,Uhlemann, A.C.,Bordone, L.A.,Han, A.,Rohde, C.H.,Ogg, G.,Moody, D.B.,Rossjohn, J.,de Jong, A.
Staphylococcal phosphatidylglycerol antigens activate human T cells via CD1a.
Nat.Immunol., 24:110-122, 2023

PubMed Abstract: 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. TetramerCD4 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.

PubMed: 36550321
DOI: 10.1038/s41590-022-01375-z

Experimental method

X-RAY DIFFRACTION (2 Å)