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

Natural killer T cells expressing 'invariant' T cell receptor a-chains (TCR alpha chains) containing variable M and joining M region V(alpha)14-J(alpha)18 (V(alpha)14i) rearrangements recognize both endogenous and microbial glycolipids in the context of CD1d. How cells expressing an invariant TCRa chain and a restricted set of TCRP chains recognize structurally diverse antigens is not clear. Here we show that a V(alpha)14i TCR recognized many alpha-linked glycolipids by means of a 'hot-spot' of germline-encoded amino acids in complementarity-determining regions 3 alpha, 1 alpha and 2 beta. This hot-spot did not shift during the recognition of structurally distinct antigens, suggesting that the V(alpha)14i TCR functions as a pattern - recognition receptor, conferring on natural killer T cells the ability to sense and respond in an innate way to pathogens displaying antigenic a-linked glycolipids.