A semi-invariant V _α10 ⁺ T cell antigen receptor defines a population of natural killer T cells with distinct glycolipid antigen–recognition properties

Abstract

Type I natural killer T cells (NKT cells) are characterized by an invariant variable region 14–joining region 18 (V _α14-V _α18) T cell antigen receptor (TCR) α-chain and recognition of the glycolipid α-galactosylceramide (α-GalCer) restricted to the antigen-presenting molecule CD1d. Here we describe a population of α-GalCer-reactive NKT cells that expressed a canonical V _α10-J _α50 TCR α-chain, which showed a preference for α-glucosylceramide (α-GlcCer) and bacterial α-glucuronic acid–containing glycolipid antigens. Structurally, despite very limited TCRα sequence identity, the V _α10 TCR–CD1d–α-GlcCer complex had a docking mode similar to that of type I TCR–CD1d–α-GalCer complexes, although differences at the antigen-binding interface accounted for the altered antigen specificity. Our findings provide new insight into the structural basis and evolution of glycolipid antigen recognition and have notable implications for the scope and immunological role of glycolipid-specific T cell responses.