A novel recognition motif of human NKT antigen receptor for a glycolipid ligand.

Murine NKT cells can recognize a-galactosylceramide (a-GalCer) in the context of a class Ib CD1d molecule. Here we show that a-GalCer can selectively activate freshly isolated human Va24 F Vb11 F cells, functionally defining the human NKT cells. The naive human NKT cell repertoire consisted of cells expressing an invariant Va24JaQ chain and a diverse array of b chains derived from a single Vb11 gene segment. Stimulation with a-GalCer expanded a polyclonal subset of the human NKT cell repertoire carrying a novel complementarity-determining region (CDR) 3b consensus motif that may directly interact with the sugar moiety of a-GalCer. Our data suggest that certain redundancy is allowed for CDR3b of NKT antigen receptor to interact with the ligand and provide a first clue to understand the novel protein‐carbohydrate interaction mechanisms.