Synthesis of dideoxymycobactin antigens presented by CD1a reveals T cell fine specificity for natural lipopeptide structures.

ABSTRACT: Mycobacterium tuberculosis survival in cells requires mycobactin siderophores. Recently, the search for lipid antigens presented by the CD1a antigen-presenting protein led to the discovery of a mycobactin-like compound, dideoxymycobactin (DDM). Here we synthesize DDMs using solution phase and solid phase peptide synthesis chemistry. Comparison of synthetic standards to natural mycobacterial mycobactins by nuclear magnetic resonance and mass spectrometry allowed identification of an unexpected alpha-methyl serine unit in natural DDM. This finding further distinguishes these pre-siderophores as foreign compounds distinct from conventional peptides, and we provide evidence that this chemical variation influences the T cell response. One synthetic DDM recapitulated natural structures and poten

SUBMITTER: Young DC 

PROVIDER: S-EPMC2757212 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature