Crystal Structure of V delta 1 T Cell Receptor in Complex with CD1d-Sulfatide Shows MHC-like Recognition of a Self-Lipid by Human gamma delta T Cells

• Published in: Immunity (Cambridge, Mass.) Vol. 39; no. 6; pp. 1032 - 1042
• Main Authors: Luoma, Adrienne M, Castro, Caitlin D, Mayassi, Toufic, Bembinster, Leslie A, Bai, Li, Picard, Damien, Anderson, Brian, Scharf, Louise, Kung, Jennifer E, Sibener, Leah V, Savage, Paul B, Jabri, Bana, Bendelac, Albert, Adams, Erin J
• Format: Journal Article
• Language: English
• Published: 12-12-2013
• ISSN: 1074-7613
• DOI: 10.1016/j.immuni.2013.11.001

The nature of the antigens recognized by gamma delta T cells and their potential recognition of major histocompatibility complex (MHC)-like molecules has remained unclear. Members of the CD1 family of lipid-presenting molecules are suggested ligands for V delta 1 TCR-expressing gamma delta T cells, the major gamma delta lymphocyte population in epithelial tissues. We crystallized a V delta 1 TCR in complex with CD1d and the self-lipid sulfatide, revealing the unusual recognition of CD1d by germline V delta 1 residues spanning all complementarity-determining region (CDR) loops, as well as sulfatide recognition separately encoded by nongermline CDR3 delta residues. Binding and functional analysis showed that CD1d presenting self-lipids, including sulfatide, was widely recognized by gut V delta 1+ gamma delta T cells. These findings provide structural demonstration of MHC-like recognition of a self-lipid by gamma delta T cells and reveal the prevalence of lipid recognition by innate-like T cell populations.