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Reconstitution by MHC-restricted peptides of HLA-A2 heavy chain with beta 2-microglobulin, in vitro 总被引:6,自引:0,他引:6
Cytotoxic T lymphocytes kill virally infected cells when they detect antigenic fragments presented by class I major histocompatibility complex (MHC) antigens (HLA in humans). The crystal structures of HLA-A2 and HLA-Aw68 reveal that peptide-antigen forms an integral part of the HLA structure, being retained in a prominent groove even after purification and crystallization. Here we report that the heavy chain and beta 2-microglobulin of HLA-A2, after separation and fractionation in denaturants, reassemble efficiently under renaturing conditions only in the presence of MHC-restricted peptides. A complex of heavy chain, beta 2-microglobulin, and viral peptide in the ratio 1:1:1 is formed in up to 46% yield. Reconstitution is not stimulated by either of two peptides not restricted to HLA-A2. The reconstituted complex of HLA-A2 and the influenza virus (B/Lee/40) nucleoprotein peptide, Np (85-94), crystallizes under conditions previously used to crystallize HLA-A2. Peptide-linked folding and assembly suggests mechanisms for the unusual capacity of HLA to bind many peptides of diverse sequence. 相似文献
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Reich D Patterson N De Jager PL McDonald GJ Waliszewska A Tandon A Lincoln RR DeLoa C Fruhan SA Cabre P Bera O Semana G Kelly MA Francis DA Ardlie K Khan O Cree BA Hauser SL Oksenberg JR Hafler DA 《Nature genetics》2005,37(10):1113-1118
Multiple sclerosis is a common disease with proven heritability, but, despite large-scale attempts, no underlying risk genes have been identified. Traditional linkage scans have so far identified only one risk haplotype for multiple sclerosis (at HLA on chromosome 6), which explains only a fraction of the increased risk to siblings. Association scans such as admixture mapping have much more power, in principle, to find the weak factors that must explain most of the disease risk. We describe here the first high-powered admixture scan, focusing on 605 African American cases and 1,043 African American controls, and report a locus on chromosome 1 that is significantly associated with multiple sclerosis. 相似文献
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The mechanism responsible for the triggering of earthquakes remains one of the least-understood aspects of the earthquake process. The magnitude-7.3 Landers, California earthquake of 28 June 1992 was followed for several weeks by triggered seismic activity over a large area, encompassing much of the western United States. Here we show that this triggered seismicity marked the beginning of a five-year trend, consisting of an elevated microearthquake rate that was modulated by an annual cycle, decaying with time. The annual cycle is mainly associated with several hydrothermal or volcanic regions where short-term triggering was also observed. These data indicate that the Landers earthquake produced long-term physical changes in these areas, and that an environmental source of stress--plausibly barometric pressure--might be responsible for the annual variation. 相似文献
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Résumé On a injecté du LSD-25, de l'acide bromolysergique-diéthylamide et de l'acided-lysergique à desDrosophila pseudoobscura au troisième stade larvaire. Le LSD-25 n'affecte ni leur capacité de ponte, lorsqu'elles sont adultes, ni la viabilité (rapport numérique adultes/ufs) de leur progéniture. En revanche, la capacité de ponte est réduite tant par l'acide lysergique que par l'acide bromolysergique-diéthylamide, et ce dernier altère en outre la viabilité. 相似文献
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K. L. Hintze Ann Baker Grow L. J. Fischer 《Cellular and molecular life sciences : CMLS》1977,33(11):1495-1497
Summary Hypophysectomized rats given cyproheptadine (40 mg/kg) for 10 days exhibited a loss of pancreatic immunoreactive insulin and ultrastructural changes in the cytoplasm of beta-cells. Sham-operated animals given cyproheptadine showed identical changes in pancreatic beta-cells except that cytoplasmic involvement progressed to the formation of large vacuoles. The pituitary is not directly involved with the cyproheptadine-induced depletion of pancreatic insulin but plays a role in the formation of large cytoplasmic vacuoles.Acknowledgments. This work was supported by U. S. Public Health Service, grant GM 12675. 相似文献