T cell receptor CDR2beta and CDR3beta loops collaborate functionally to shape the iNKT cell repertoire

Thierry Mallevaey, James P Scott-Browne, Jennifer L Matsuda, Mary H Young, Daniel G Pellicci, Onisha Patel, Meena Thakur, Lars Kjer-Nielsen, Stewart K Richardson, Vincenzo Cerundolo, Amy R Howell, James McCluskey, Dale I Godfrey, Jamie Rossjohn, Philippa Marrack, Laurent Gapin

Research output: Contribution to journalArticleResearchpeer-review

79 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)60 - 71
Number of pages12
JournalImmunity
Volume31
Issue number1
DOIs
Publication statusPublished - 2009

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