Human Gamma Delta T Cells Recognize Cd1b By Two Distinct Mechanisms

gamma delta T cells form an abundant part of the human cellular immune system, where they respond to tissue damage, infection, and cancer. The spectrum of known molecular targets recognized by V delta 1-expressing gamma delta T cells is becoming increasingly diverse. Here we describe human gamma delta T cells that recognize CD1b, a lipid antigenpresenting molecule, which is inducibly expressed on monocytes and dendritic cells. Using CD1b tetramers to study multiple donors, we found that many CD1b-specific gamma delta T cells use V delta 1. Despite their common use of V delta 1, three CD1b-specific gamma delta T cell receptors (TCRs) showed clear differences in the surface of CD1b recognized, the requirement for lipid antigens, and corecognition of butryophilinlike proteins. Several V. segments were present among the CD1bspecific TCRs, but chain swap experiments demonstrated that CD1b specificity was mediated by the V delta 1 chain. One of the CD1b-specific V delta 1(+) TCRs paired with V gamma 4 and shows dual reactivity to CD1b and butyrophilin-like proteins. alpha beta TCRs typically recognize the peptide display platform of MHC proteins. In contrast, our results demonstrate the use of rearranged receptors to mediate diverse modes of recognition across the surface of CD1b in ways that do and do not require carried lipids.