@article{93c60742c3854132bece2d5ad67e6b4a,
title = "A molecular basis for the exquisite CD1d-restricted antigen specificity and functional responses of natural killer T cells",
abstract = "Natural killer T (NKT) cells respond to a variety of CD1d-restricted antigens (Ags), although the basis for Ag discrimination by the NKT cell receptor (TCR) is unclear. Here we have described NKT TCR fine specificity against several closely related Ags, termed altered glycolipid ligands (AGLs), which differentially stimulate NKT cells. The structures of five ternary complexes all revealed similar docking. Acyl chain modifications did not affect the interaction, but reduced NKT cell proliferation, indicating an affect on Ag processing or presentation. Conversely, truncation of the phytosphingosine chain caused an induced fit mode of TCR binding that affected TCR affinity. Modifications in the glycosyl head group had a direct impact on the TCR interaction and associated cellular response, with ligand potency reflecting the t1/2 life of the interaction. Accordingly, we have provided a molecular basis for understanding how modifications in AGLs can result in striking alterations in the cellular response of NKT cells.",
author = "Wun, {Kwok S.} and Garth Cameron and Onisha Patel and Pang, {Siew Siew} and Pellicci, {Daniel G.} and Sullivan, {Lucy C.} and Santosh Keshipeddy and Young, {Mary H.} and Uldrich, {Adam P.} and Thakur, {Meena S.} and Richardson, {Stewart K.} and Howell, {Amy R.} and Illarionov, {Petr A.} and Brooks, {Andrew G.} and Besra, {Gurdyal S.} and James McCluskey and Laurent Gapin and Porcelli, {Steven A.} and Godfrey, {Dale I.} and Jamie Rossjohn",
note = "Funding Information: We thank the staff at the Australian synchrotron for assistance with data collection. We also thank D. Taylor, S. Chakravarti, and K. Field for assistance. We are grateful to P. Savage for generously providing α-GalCer (PBS44) for CD1d tetramer loading. This work was supported by the Cancer Council of Victoria, the National Health and Medical Research Council of Australia (NHMRC), and the Australian Research Council. G.C. is supported by CRI predoctoral scholarship and L.C.S. by an NHMRC RD Wright Fellowship. S.A.P. was supported by NIH grant AI45889. A.R.H. was supported by NIH grant R01GM087136. L.G. is supported by NIH grants (AI076463 and AI078246) and M.H.Y. by NIH training grant T32 AI07405. D.I.G. is supported by an NHMRC Principal Research Fellowship; J.R. is supported by an ARC Federation Fellowship. S.A.P. has received payments as a consultant for Vaccinex, Inc. (Rochester, NY) for work related to the development of therapeutics based on CD1d-pretreated glycolipids. ",
year = "2011",
month = mar,
day = "25",
doi = "10.1016/j.immuni.2011.02.001",
language = "English (US)",
volume = "34",
pages = "327--339",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "3",
}
