Molecular Analysis of Lipid-Reactive Vδ1 γδ T Cells Identified by CD1c Tetramers.

CDlc 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 CDlc tetramers carrying Mycobacterium tuberculosis phosphomycoketide bind γδ TCRs. An unbiased method of ligand-based I CR selection detects interactions only with Vδ1+ TCRs, and mutational analyses demonstrate a role of the Vδ1 domain during recognition. These results strengthen evidence for a role of CDlc in the γδ T cell response, providing biophysical evidence for CDlc-γδ TCR interactions and a named foreign Ag. Surprisingly, TCRs also bind CDlc complexes formed with diverse lipids such as lysophosphatidylcholine, sulfatide, or mannosyl-phosophomycoketide, but not lipopeptide ligands. Dissection of TCR interactions with CDlc 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. [ABSTRACT FROM AUTHOR]