T cell receptor CDR2 beta and CDR3 beta loops collaborate functionally to shape the iNKT cell repertoire.
Mouse type I natural killer T cell receptors (iNKT TCRs) use a single V alpha 14-J alpha 18 sequence and V beta s that are almost always V beta 8.2, V beta 7, or V beta 2, although the basis of this differential usage is unclear. We showed that the V beta bias occurred as a consequence of the CDR2 beta loops determining the affinity of the iNKT TCR for CD1d-glycolipids, thus controlling positive selection. Within a conserved iNKT-TCR-CD1d docking framework, these inherent V beta-CD1d affinities are further modulated by the hypervariable CDR3 beta loop, thereby defining a functional interplay between the two iNKT TCR CDR beta loops. These V beta biases revealed a broadly hierarchical response in which V beta 8.2 > V beta 7 > V beta 2 in the recognition of diverse CD1d ligands. This restriction of the iNKT TCR repertoire during thymic selection paradoxically ensures that each peripheral iNKT cell recognizes a similar spectrum of antigens.
Mallevaey
Thierry
T
Department of Immunology, University of Colorado Denver and National Jewish Health, Denver, CO 80206, USA.
Scott-Browne
James P
JP
Matsuda
Jennifer L
JL
Young
Mary H
MH
Pellicci
Daniel G
DG
Patel
Onisha
O
Thakur
Meena
M
Kjer-Nielsen
Lars
L
Richardson
Stewart K
SK
Cerundolo
Vincenzo
V
Howell
Amy R
AR
McCluskey
James
J
Godfrey
Dale I
DI
Rossjohn
Jamie
J
Marrack
Philippa
P
Gapin
Laurent
L
D000818:Animals; D055610:Antigens, CD1d / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology
D055610:Antigens, CD1d; D016693:Receptors, Antigen, T-Cell, alpha-beta