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

Nat Immunol. 2007 Oct;8(10):1105-13. doi: 10.1038/ni1510. Epub 2007 Sep 9.


Natural killer T cells expressing 'invariant' T cell receptor alpha-chains (TCRalpha chains) containing variable (V) and joining (J) 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 TCRalpha chain and a restricted set of TCRbeta 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 3alpha, 1alpha and 2beta. 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 alpha-linked glycolipids.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD1 / chemistry
  • Antigens, CD1 / immunology
  • Antigens, CD1d
  • Complementarity Determining Regions
  • Crystallography
  • Galactosylceramides / chemistry
  • Galactosylceramides / immunology*
  • Immunity, Innate
  • Killer Cells, Natural / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Antigen, T-Cell, alpha-beta / chemistry
  • Receptors, Antigen, T-Cell, alpha-beta / physiology*


  • Antigens, CD1
  • Antigens, CD1d
  • Complementarity Determining Regions
  • Galactosylceramides
  • Receptors, Antigen, T-Cell, alpha-beta
  • alpha-galactosylceramide