title: T cell receptor CDR2 beta and CDR3 beta loops collaborate functionally to shape the iNKT cell repertoire.
abstract: 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.
authors: Department of Immunology, University of Colorado Denver and National Jewish Health, Denver, CO 80206, USA.
authors: Thierry
authors: T
authors: Mallevaey
authors: James P
authors: JP
authors: Scott-Browne
authors: Jennifer L
authors: JL
authors: Matsuda
authors: Mary H
authors: MH
authors: Young
authors: Daniel G
authors: DG
authors: Pellicci
authors: Onisha
authors: O
authors: Patel
authors: Meena
authors: M
authors: Thakur
authors: Lars
authors: L
authors: Kjer-Nielsen
authors: Stewart K
authors: SK
authors: Richardson
authors: Vincenzo
authors: V
authors: Cerundolo
authors: Amy R
authors: AR
authors: Howell
authors: James
authors: J
authors: McCluskey
authors: Dale I
authors: DI
authors: Godfrey
authors: Jamie
authors: J
authors: Rossjohn
authors: Philippa
authors: P
authors: Marrack
authors: Laurent
authors: L
authors: Gapin
mesh_terms: 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
chemical_list: D055610:Antigens, CD1d; D016693:Receptors, Antigen, T-Cell, alpha-beta