7sh4

CD1a-phosphatidylglycerol binary structureCD1a-phosphatidylglycerol binary structure

Structural highlights

7sh4 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CD1A_HUMAN Antigen-presenting protein that binds self and non-self lipid and glycolipid antigens and presents them to T-cell receptors on natural killer T-cells.^[1] ^[2] ^[3]

Publication Abstract from PubMed

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.

Staphylococcal phosphatidylglycerol antigens activate human T cells via CD1a.,Monnot GC, Wegrecki M, Cheng TY, Chen YL, Sallee BN, Chakravarthy R, Karantza IM, Tin SY, Khaleel AE, Monga I, Uwakwe LN, Tillman A, Cheng B, Youssef S, Ng SW, Shahine A, Garcia-Vilas JA, Uhlemann AC, Bordone LA, Han A, Rohde CH, Ogg G, Moody DB, Rossjohn J, de Jong A Nat Immunol. 2023 Jan;24(1):110-122. doi: 10.1038/s41590-022-01375-z. Epub 2022 , Dec 22. PMID:36550321^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Salamero J, Bausinger H, Mommaas AM, Lipsker D, Proamer F, Cazenave JP, Goud B, de la Salle H, Hanau D. CD1a molecules traffic through the early recycling endosomal pathway in human Langerhans cells. J Invest Dermatol. 2001 Mar;116(3):401-8. PMID:11231314 doi:1264
↑ Vincent MS, Xiong X, Grant EP, Peng W, Brenner MB. CD1a-, b-, and c-restricted TCRs recognize both self and foreign antigens. J Immunol. 2005 Nov 15;175(10):6344-51. PMID:16272286
↑ Sloma I, Zilber MT, Vasselon T, Setterblad N, Cavallari M, Mori L, De Libero G, Charron D, Mooney N, Gelin C. Regulation of CD1a surface expression and antigen presentation by invariant chain and lipid rafts. J Immunol. 2008 Jan 15;180(2):980-7. PMID:18178838
↑ Monnot GC, Wegrecki M, Cheng TY, Chen YL, Sallee BN, Chakravarthy R, Karantza IM, Tin SY, Khaleel AE, Monga I, Uwakwe LN, Tillman A, Cheng B, Youssef S, Ng SW, Shahine A, Garcia-Vilas JA, Uhlemann AC, Bordone LA, Han A, Rohde CH, Ogg G, Moody DB, Rossjohn J, de Jong A. Staphylococcal phosphatidylglycerol antigens activate human T cells via CD1a. Nat Immunol. 2023 Jan;24(1):110-122. PMID:36550321 doi:10.1038/s41590-022-01375-z

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OCA

[1] Salamero J, Bausinger H, Mommaas AM, Lipsker D, Proamer F, Cazenave JP, Goud B, de la Salle H, Hanau D. CD1a molecules traffic through the early recycling endosomal pathway in human Langerhans cells. J Invest Dermatol. 2001 Mar;116(3):401-8. PMID:11231314 doi:1264

[2] Vincent MS, Xiong X, Grant EP, Peng W, Brenner MB. CD1a-, b-, and c-restricted TCRs recognize both self and foreign antigens. J Immunol. 2005 Nov 15;175(10):6344-51. PMID:16272286

[3] Sloma I, Zilber MT, Vasselon T, Setterblad N, Cavallari M, Mori L, De Libero G, Charron D, Mooney N, Gelin C. Regulation of CD1a surface expression and antigen presentation by invariant chain and lipid rafts. J Immunol. 2008 Jan 15;180(2):980-7. PMID:18178838

[4] Monnot GC, Wegrecki M, Cheng TY, Chen YL, Sallee BN, Chakravarthy R, Karantza IM, Tin SY, Khaleel AE, Monga I, Uwakwe LN, Tillman A, Cheng B, Youssef S, Ng SW, Shahine A, Garcia-Vilas JA, Uhlemann AC, Bordone LA, Han A, Rohde CH, Ogg G, Moody DB, Rossjohn J, de Jong A. Staphylococcal phosphatidylglycerol antigens activate human T cells via CD1a. Nat Immunol. 2023 Jan;24(1):110-122. PMID:36550321 doi:10.1038/s41590-022-01375-z

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[2]

[3]

[4]

7sh4

CD1a-phosphatidylglycerol binary structureCD1a-phosphatidylglycerol binary structure

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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7sh4

CD1a-phosphatidylglycerol binary structureCD1a-phosphatidylglycerol binary structure

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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