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Find video protocols related to scientific articles indexed in Pubmed.
A molecular basis for the exquisite CD1d-restricted antigen specificity and functional responses of natural killer T cells.
Immunity
PUBLISHED: 01-31-2011
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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 t(1/2) 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.
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Carbocyclization of carbohydrates: diastereoselective synthesis of (+)-gabosine F, (-)-gabosine O, and (+)-4-epi-gabosine O.
Org. Lett.
PUBLISHED: 10-07-2009
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Exploitation of silica gel/chloramine T mediated intramolecular nitrile oxide-alkene cycloaddition (INOC) of sugar-derived oximes to carbocycles furnished the first synthesis of gabosine F from l-arabinose in 12 steps with 23% overall yield, thereby confirming its absolute configuration. Similarly, efficient syntheses of gabosine O and 4-epi-gabosine O were accomplished from D-mannose in 9 and 11 steps with 41% and 38% overall yields, respectively, involving INOC, regioselective dehydration, and diastereoselective hydrogenation as the key steps.
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Human and mouse type I natural killer T cell antigen receptors exhibit different fine specificities for CD1d-antigen complex.
J. Biol. Chem.
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Human and mouse type I natural killer T (NKT) cells respond to a variety of CD1d-restricted glycolipid antigens (Ags), with their NKT cell antigen receptors (NKT TCRs) exhibiting reciprocal cross-species reactivity that is underpinned by a conserved NKT TCR-CD1d-Ag docking mode. Within this common docking footprint, the NKT TCR recognizes, to varying degrees of affinity, a range of Ags. Presently, it is unclear whether the human NKT TCRs will mirror the generalities underpinning the fine specificity of the mouse NKT TCR-CD1d-Ag interaction. Here, we assessed human NKT TCR recognition against altered glycolipid ligands of ?-galactosylceramide (?-GalCer) and have determined the structures of a human NKT TCR in complex with CD1d-4,4?-deoxy-?-GalCer and CD1d-?-GalCer with a shorter, di-unsaturated acyl chain (C20:2). Altered glycolipid ligands with acyl chain modifications did not affect the affinity of the human NKT TCR-CD1d-Ag interaction. Surprisingly, human NKT TCR recognition is more tolerant to modifications at the 4-OH position in comparison with the 3-OH position of ?-GalCer, which contrasts the fine specificity of the mouse NKT TCR-CD1d-Ag recognition (4-OH > 3-OH). The fine specificity differences between human and mouse NKT TCRs was attributable to differing interactions between the respective complementarity-determining region 1? loops and the Ag. Accordingly, germline encoded fine-specificity differences underpin human and mouse type I NKT TCR interactions, which is an important consideration for therapeutic development and NKT cell physiology.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.