Differential recognition of CD1d-alpha-galactosyl ceramide by the V beta 8.2 and V beta 7 semi-invariant NKT T cell receptors.
The semi-invariant natural killer T cell receptor (NKT TCR) recognizes CD1d-lipid antigens. Although the TCR alpha chain is typically invariant, the beta chain expression is more diverse, where three V beta chains are commonly expressed in mice. We report the structures of V alpha 14-V beta 8.2 and V alpha 14-V beta 7 NKT TCRs in complex with CD1d-alpha-galactosylceramide (alpha-GalCer) and the 2.5 A structure of the human NKT TCR-CD1d-alpha-GalCer complex. Both V beta 8.2 and V beta 7 NKT TCRs and the human NKT TCR ligated CD1d-alpha-GalCer in a similar manner, highlighting the evolutionarily conserved interaction. However, differences within the V beta domains of the V beta 8.2 and V beta 7 NKT TCR-CD1d complexes resulted in altered TCR beta-CD1d-mediated contacts and modulated recognition mediated by the invariant alpha chain. Mutagenesis studies revealed the differing contributions of V beta 8.2 and V beta 7 residues within the CDR2 beta loop in mediating contacts with CD1d. Collectively we provide a structural basis for the differential NKT TCR V beta usage in NKT cells.
Pellicci
Daniel G
DG
Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia.
Patel
Onisha
O
Kjer-Nielsen
Lars
L
Pang
Siew Siew
SS
Sullivan
Lucy C
LC
Kyparissoudis
Konstantinos
K
Brooks
Andrew G
AG
Reid
Hugh H
HH
Gras
Stephanie
S
Lucet
Isabelle S
IS
Koh
Ruide
R
Smyth
Mark J
MJ
Mallevaey
Thierry
T
Matsuda
Jennifer L
JL
Gapin
Laurent
L
McCluskey
James
J
Godfrey
Dale I
DI
Rossjohn
Jamie
J
D000818:Animals; D055610:Antigens, CD1d / Q000737:chemistry / Q000276:immunology*; D003001:Cloning, Molecular; D003460:Crystallization; D005699:Galactosylceramides / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D051379:Mice; D016296:Mutagenesis; D055611:Natural Killer T-Cells / Q000276:immunology*; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D011487:Protein Conformation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
D055610:Antigens, CD1d; D005699:Galactosylceramides; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; C109168:T-cell receptor Vbeta 8.2; C493154:alpha-galactosylceramide