Adaptability of the semi-invariant natural killer T-cell receptor towards structurally diverse CD1d-restricted ligands.
The semi-invariant natural killer (NK) T-cell receptor (NKTcr) recognises structurally diverse glycolipid antigens presented by the monomorphic CD1d molecule. While the alpha-chain of the NKTcr is invariant, the beta-chain is more diverse, but how this diversity enables the NKTcr to recognise diverse antigens, such as an alpha-linked monosaccharide (alpha-galactosylceramide and alpha-galactosyldiacylglycerol) and the beta-linked trisaccharide (isoglobotriaosylceramide), is unclear. We demonstrate here that NKTcrs, which varied in their beta-chain usage, recognised diverse glycolipid antigens with a similar binding mode on CD1d. Nevertheless, the NKTcrs recognised distinct epitopic sites within these antigens, including alpha-galactosylceramide, the structurally similar alpha-galactosyldiacylglycerol and the very distinct isoglobotriaosylceramide. We also show that the relative roles of the CDR loops within the NKTcr beta-chain varied as a function of the antigen. Thus, while NKTcrs characteristically use a conserved docking mode, the NKTcr beta-chain allows these cells to recognise unique aspects of structurally diverse CD1d-restricted ligands.
Florence
William C
WC
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA.
Xia
Chengfeng
C
Gordy
Laura E
LE
Chen
Wenlan
W
Zhang
Yalong
Y
Scott-Browne
James
J
Kinjo
Yuki
Y
Yu
Karl O A
KO
Keshipeddy
Santosh
S
Pellicci
Daniel G
DG
Patel
Onisha
O
Kjer-Nielsen
Lars
L
McCluskey
James
J
Godfrey
Dale I
DI
Rossjohn
Jamie
J
Richardson
Stewart K
SK
Porcelli
Steven A
SA
Howell
Amy R
AR
Hayakawa
Kyoko
K
Gapin
Laurent
L
Zajonc
Dirk M
DM
Wang
Peng George
PG
Joyce
Sebastian
S
D000220:Adaptation, Biological / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D055610:Antigens, CD1d / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology; D002478:Cells, Cultured; D005699:Galactosylceramides / Q000737:chemistry / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D055611:Natural Killer T-Cells / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology / Q000378:metabolism; D013329:Structure-Activity Relationship; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology
D055610:Antigens, CD1d; D015295:Antigens, Tumor-Associated, Carbohydrate; D005699:Galactosylceramides; C472766:Gb3 antigen; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; C493154:alpha-galactosylceramide