Molecular Analysis of Lipid-Reactive V?1 ?? T Cells Identified by CD1c Tetramers.

ABSTRACT: CD1c is abundantly expressed on human dendritic cells (DC) and B cells, where it binds and displays lipid Ags to T cells. In this study, we report that CD1c tetramers carrying Mycobacterium tuberculosis phosphomycoketide bind ?? TCRs. An unbiased method of ligand-based TCR selection detects interactions only with V?1(+) TCRs, and mutational analyses demonstrate a role of the V?1 domain during recognition. These results strengthen evidence for a role of CD1c in the ?? T cell response, providing biophysical evidence for CD1c-?? TCR interactions and a named foreign Ag. Surprisingly, TCRs also bind CD1c complexes formed with diverse lipids such as lysophosphatidylcholine, sulfatide, or mannosyl-phosophomycoketide, but not lipopeptide ligands. Dissection of TCR interactions with CD1c carrying foreign Ags, permissive ligands, and nonpermissive lipid ligands clarifies the molecular basis of the frequently observed but poorly understood phenomenon of mixed self- and foreign Ag reactivity in the CD1 system.

SUBMITTER: Roy S 

PROVIDER: S-EPMC4744554 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature