Strategy of lipid recognition by invariant natural killer T cells: ‘one for all and all for one’
Version of Record online: 1 JUN 2012
© 2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd
Volume 136, Issue 3, pages 273–282, July 2012
How to Cite
Mallevaey, T. and Selvanantham, T. (2012), Strategy of lipid recognition by invariant natural killer T cells: ‘one for all and all for one’. Immunology, 136: 273–282. doi: 10.1111/j.1365-2567.2012.03580.x
- Issue online: 1 JUN 2012
- Version of Record online: 1 JUN 2012
- Received 17 January 2012; revised 14 February 2012; accepted 14 February 2012.
- lipid antigens;
- natural killer T cells;
- T-cell receptor
Invariant natural killer T (iNKT) cells are evolutionarily conserved lipid-reactive T cells that bridge innate and adaptive immune responses. Despite a relatively restricted T-cell receptor (TCR) diversity, these cells respond to a variety of structurally distinct foreign (i.e. microbial or synthetic) as well as host-derived (self-) lipid antigens presented by the CD1d molecule. These multi-tasking lymphocytes are among the first responders in immunity, and produce an impressive array of cytokines and chemokines that can tailor the ensuing immune response. Accordingly, iNKT cells play important functions in autoimmune diseases, cancer, infection and inflammation. These properties make iNKT cells appealing targets in immune-based therapies. Yet, much has to be learned on the mechanisms that allow iNKT cells to produce polarized responses. Responses of iNKT cells are influenced by the direct signals perceived by the cells through their TCRs, as well as by indirect co-stimulatory (and potentially co-inhibitory) cues that they receive from antigen-presenting cells or the local milieu. A decade ago, biochemists and immunologists have started to describe synthetic lipid agonists with cytokine skewing potential, paving a new research avenue in the iNKT cell field. Yet how iNKT cells translate various antigenic signals into distinct functional responses has remained obscure. Recent findings have revealed a unique and innate mode of lipid recognition by iNKT cells, and suggest that both the lipid antigen presented and the diversity of the TCR modulate the strength of CD1d-iNKT TCR interactions. In this review, we focus on novel discoveries on lipid recognition by iNKT cells, and how these findings may help us to design effective strategies to steer iNKT cell responses for immune intervention.