Germline-encoded recognition of diverse glycolipids by natural killer T cells

Abstract

Natural killer T cells expressing 'invariant' T cell receptor α-chains (TCRα chains) containing variable (V) and joining (J) region Vα14-Jα18 (Vα14i) rearrangements recognize both endogenous and microbial glycolipids in the context of CD1d. How cells expressing an invariant TCRα chain and a restricted set of TCRα chains recognize structurally diverse antigens is not clear. Here we show that a Vα14i TCR recognized many α-linked glycolipids by means of a 'hot-spot' of germline-encoded amino acids in complementarity-determining regions 3α, 1α and 2β. This hot-spot did not shift during the recognition of structurally distinct antigens, suggesting that the Vα14i TCR functions as a pattern-recogni..