The 2.5 Å Structure of CD1c in Complex with a Mycobacterial Lipid Reveals an Open Groove Ideally Suited for Diverse Antigen Presentation

Journal Article · Wed Aug 24 04:00:00 EDT 2011 · Immunity

DOI:https://doi.org/10.1016/j.immuni.2010.11.026· OSTI ID:1023045

Scharf, Louise; Li, Nan-Sheng; Hawk, Andrew J; Garzón, Diana; Zhang, Tejia; Fox, Lisa M; Kazen, Allison R; Shah, Sneha; Haddadian, Esmael J; Gumperz, Jenny E; Saghatelian, Alan; Faraldo-Gómez, José D; Meredith, Stephen C; Piccirilli, Joseph A; Adams, Erin J ^[1]

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1. Harvard

CD1 molecules function to present lipid-based antigens to T cells. Here we present the crystal structure of CD1c at 2.5 {angstrom} resolution, in complex with the pathogenic Mycobacterium tuberculosis antigen mannosyl-{beta}1-phosphomycoketide (MPM). CD1c accommodated MPM's methylated alkyl chain exclusively in the A pocket, aided by a unique exit portal underneath the {alpha}1 helix. Most striking was an open F pocket architecture lacking the closed cavity structure of other CD1 molecules, reminiscent of peptide binding grooves of classical major histocompatibility complex molecules. This feature, combined with tryptophan-fluorescence quenching during loading of a dodecameric lipopeptide antigen, provides a compelling model by which both the lipid and peptide moieties of the lipopeptide are involved in CD1c presentation of lipopeptides.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: USDOE Office of Science (SC)
• OSTI ID: 1023045
• Journal Information: Immunity, Journal Name: Immunity Journal Issue: (6) ; 12, 2010 Vol. 33
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

60 APPLIED LIFE SCIENCES
ANTIGENS
ARCHITECTURE
CHAINS
CRYSTAL STRUCTURE
HISTOCOMPATIBILITY COMPLEX
LIPIDS
MYCOBACTERIUM TUBERCULOSIS
PEPTIDES
QUENCHING
RESOLUTION