Germline-encoded recognition of diverse glycolipids by natural killer T cells.
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.
Scott-Browne
James P
JP
Department of Immunology, University of Colorado Health Sciences Center and National Jewish Medical and Research Center, Denver, Colorado, 80206, USA.
Matsuda
Jennifer L
JL
Mallevaey
Thierry
T
White
Janice
J
Borg
Natalie A
NA
McCluskey
James
J
Rossjohn
Jamie
J
Kappler
John
J
Marrack
Philippa
P
Gapin
Laurent
L
D000818:Animals; D018949:Antigens, CD1 / Q000737:chemistry / Q000276:immunology; D055610:Antigens, CD1d; D022801:Complementarity Determining Regions; D003461:Crystallography; D005699:Galactosylceramides / Q000737:chemistry / Q000276:immunology*; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000502:physiology*