6c09

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Ternary crystal structure of the 3C8 TCR-CD1c-monoacylglycerol complex

Structural highlights

6c09 is a 4 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 2.95Å
Ligands:D10, EDO, EKG, K, NAG, PEG
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CD1C_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] [4]

Publication Abstract from PubMed

The hallmark function of alphabeta T cell antigen receptors (TCRs) involves the highly specific co-recognition of a major histocompatibility complex molecule and its carried peptide. However, the molecular basis of the interactions of TCRs with the lipid antigen-presenting molecule CD1c is unknown. We identified frequent staining of human T cells with CD1c tetramers across numerous subjects. Whereas TCRs typically show high specificity for antigen, both tetramer binding and autoreactivity occurred with CD1c in complex with numerous, chemically diverse self lipids. Such extreme polyspecificity was attributable to binding of the TCR over the closed surface of CD1c, with the TCR covering the portal where lipids normally protrude. The TCR essentially failed to contact lipids because they were fully seated within CD1c. These data demonstrate the sequestration of lipids within CD1c as a mechanism of autoreactivity and point to small lipid size as a determinant of autoreactive T cell responses.

T cell autoreactivity directed toward CD1c itself rather than toward carried self lipids.,Wun KS, Reijneveld JF, Cheng TY, Ladell K, Uldrich AP, Le Nours J, Miners KL, McLaren JE, Grant EJ, Haigh OL, Watkins TS, Suliman S, Iwany S, Jimenez J, Calderon R, Tamara KL, Leon SR, Murray MB, Mayfield JA, Altman JD, Purcell AW, Miles JJ, Godfrey DI, Gras S, Price DA, Van Rhijn I, Moody DB, Rossjohn J Nat Immunol. 2018 Apr;19(4):397-406. doi: 10.1038/s41590-018-0065-7. Epub 2018, Mar 12. PMID:29531339[5]

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

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Citations
10 reviews cite this structure
A multilayered immune system through the lens of unconventional T cells.
Mayassi et al. (2021)
9 more
27 other articles
No citations found

See Also

References

  1. ↑ Moody DB, Ulrichs T, Muhlecker W, Young DC, Gurcha SS, Grant E, Rosat JP, Brenner MB, Costello CE, Besra GS, Porcelli SA. CD1c-mediated T-cell recognition of isoprenoid glycolipids in Mycobacterium tuberculosis infection. Nature. 2000 Apr 20;404(6780):884-8. PMID:10786796 doi:http://dx.doi.org/10.1038/35009119
  2. ↑ Sugita M, van Der Wel N, Rogers RA, Peters PJ, Brenner MB. CD1c molecules broadly survey the endocytic system. Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8445-50. PMID:10890914 doi:http://dx.doi.org/10.1073/pnas.150236797
  3. ↑ Briken V, Jackman RM, Watts GF, Rogers RA, Porcelli SA. Human CD1b and CD1c isoforms survey different intracellular compartments for the presentation of microbial lipid antigens. J Exp Med. 2000 Jul 17;192(2):281-8. PMID:10899914
  4. ↑ Scharf L, Li NS, Hawk AJ, Garzon D, Zhang T, Fox LM, Kazen AR, Shah S, Haddadian EJ, Gumperz JE, Saghatelian A, Faraldo-Gomez JD, Meredith SC, Piccirilli JA, Adams EJ. The 2.5 a structure of CD1c in complex with a mycobacterial lipid reveals an open groove ideally suited for diverse antigen presentation. Immunity. 2010 Dec 14;33(6):853-62. PMID:21167756 doi:10.1016/j.immuni.2010.11.026
  5. ↑ Wun KS, Reijneveld JF, Cheng TY, Ladell K, Uldrich AP, Le Nours J, Miners KL, McLaren JE, Grant EJ, Haigh OL, Watkins TS, Suliman S, Iwany S, Jimenez J, Calderon R, Tamara KL, Leon SR, Murray MB, Mayfield JA, Altman JD, Purcell AW, Miles JJ, Godfrey DI, Gras S, Price DA, Van Rhijn I, Moody DB, Rossjohn J. T cell autoreactivity directed toward CD1c itself rather than toward carried self lipids. Nat Immunol. 2018 Apr;19(4):397-406. doi: 10.1038/s41590-018-0065-7. Epub 2018, Mar 12. PMID:29531339 doi:http://dx.doi.org/10.1038/s41590-018-0065-7

Contents


PDB ID 6c09

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