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401.
Rachel N. Cotton Marcin Wegrecki Tan-Yun Cheng Yi-Ling Chen Natacha Veerapen Jrme Le Nours Dennis P. Orgill Bohdan Pomahac Simon G. Talbot Richard Willis John D. Altman Annemieke de Jong Ildiko Van Rhijn Rachael A. Clark Gurdyal S. Besra Graham Ogg Jamie Rossjohn D. Branch Moody 《The Journal of experimental medicine》2021,218(7)
We optimized lipidomics methods to broadly detect endogenous lipids bound to cellular CD1a proteins. Whereas membrane phospholipids dominate in cells, CD1a preferentially captured sphingolipids, especially a C42, doubly unsaturated sphingomyelin (42:2 SM). The natural 42:2 SM but not the more common 34:1 SM blocked CD1a tetramer binding to T cells in all human subjects tested. Thus, cellular CD1a selectively captures a particular endogenous lipid that broadly blocks its binding to TCRs. Crystal structures show that the short cellular SMs stabilized a triad of surface residues to remain flush with CD1a, but the longer lipids forced the phosphocholine group to ride above the display platform to hinder TCR approach. Whereas nearly all models emphasize antigen-mediated T cell activation, we propose that the CD1a system has intrinsic autoreactivity and is negatively regulated by natural endogenous inhibitors selectively bound in its cleft. Further, the detailed chemical structures of natural blockers could guide future design of therapeutic blockers of CD1a response. 相似文献
402.
Krencz Ildiko Sztankovics Daniel Danko Titanilla Sebestyen Anna Khoor Andras 《Cancer metastasis reviews》2021,40(4):1141-1157
Cancer and Metastasis Reviews - Small cell lung carcinoma (SCLC) is characterized by high metastatic rate and poor prognosis. The platinum-based chemotherapy still represents the backbone of the... 相似文献
403.
The discovery of the CD1 antigen-presenting system reveals that T cells survey the lipid content of target cells via T-cell receptor (TCR) contact with CD1 bound to lipids, glycolipids and small molecules. Recently, CD1 proteins have been found to present mycobacterial lipopeptides that are involved in scavenging iron from infected cells. The mechanism of lipopeptide antigen presentation by CD1 involves the anchoring of antigens in the hydrophobic binding groove, resulting in exposure of the peptide moiety for TCR contact. These findings expand the range of known antigens for T cells and raise the intriguing possibility that CD1, similar to MHC class I and II molecules, enables T cells to discriminate among peptide sequences. 相似文献
404.
Thyroglobulin level at week 16 of pregnancy is superior to urinary iodine concentration in revealing preconceptual and first trimester iodine supply 下载免费PDF全文
Monika Katko Andrea Anett Gazso Ildiko Hircsu Harjit Pal Bhattoa Zsuzsanna Molnar Bela Kovacs David Andrasi Janos Aranyosi Rita Makai Lajos Veress Olga Torok Miklos Bodor Laszlo Samson Endre V. Nagy 《Maternal & child nutrition》2018,14(1)
Pregnant women are prone to iodine deficiency due to the increased need for iodine during gestation. Progress has recently occurred in establishing serum thyroglobulin (Tg) as an iodine status biomarker, but there is no accepted reference range for iodine sufficiency during pregnancy. An observational study was conducted in 164 pregnant women. At week 16 of gestation urinary iodine concentration (UIC), serum Tg, and thyroid functions were measured, and information on the type of iodine supplementation and smoking were recorded. The parameters of those who started iodine supplementation (≥150 μg/day) at least 4 weeks before pregnancy (n = 27), who started at the detection of pregnancy (n = 51), and who had no iodine supplementation (n = 74) were compared. Sufficient iodine supply was found in the studied population based on median UIC (162 μg/L). Iodine supplementation ≥150 μg/day resulted in higher median UIC regardless of its duration (nonusers: 130 μg/L vs. prepregnancy iodine starters: 240 μg/L, and pregnancy iodine starters: 205 μg/L, p < .001, and p = .023, respectively). Median Tg value of pregnancy starters was identical to that of nonusers (14.5 vs. 14.6 μg/L), whereas prepregnancy starters had lower median Tg (9.1 μg/L, p = .018). Serum Tg concentration at week 16 of pregnancy showed negative relationship (p = .010) with duration of iodine supplementation and positive relationship (p = .008) with smoking, a known interfering factor of iodine metabolism, by multiple regression analysis. Serum Tg at week 16 of pregnancy may be a promising biomarker of preconceptual and first trimester maternal iodine status, the critical early phase of foetal brain development. 相似文献