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    • 2. 发明申请
    • MANNOSYLATED PEPTIDES
    • 人造胶原蛋白
    • WO1998013378A1
    • 1998-04-02
    • PCT/NL1997000536
    • 1997-09-25
    • RIJKSUNIVERSITEIT TE LEIDENKONING, FritsDRIJFHOUT, Jan, Wouter
    • RIJKSUNIVERSITEIT TE LEIDEN
    • C07K14/35
    • C07K14/70539C07K9/00
    • T cells mediate specific immune reactions. They recognize (foreign) protein fragments - peptides - that are bound in the peptide binding groove of MHC molecules. These peptide MHC complexes are generated intracellularly and subsquently transported to the cell surface for recognition by T cells. A rate limiting step in the MHC restricted presentation of (foreign) peptides derived from extracellular sources is therefore the uptake of such antigens by antigen presenting cells and the delivery to the intracellular compartment(s) where the MHC-peptide complexes are formed. Professional antigen presenting cells like dendritic cells and macrophages take up antigens by macropinocytosis and mannose receptor mediated endocytosis. We have explored the possibility that the mannosylation of otherwise non-mannosylated antigens would lead to enhanced uptake and MHC restricted presentation of (fragments of) such antigens by mannose receptor positive cells. Using mannose receptor positive cultured human dendritic cells as antigen presenting cells we found that the mannosylation of antigenic peptides resulted in a 300 - 10.000 fold enhanced potency to stimulate MHC class II restricted peptide-specific T cell clones compared to non-mannosylated peptides. These results indicate that mannosylation of antigens leads to selective targeting and subsequent superior presentation by dendritic cells, a result which may be applicable in for example vaccine design.
    • T细胞介导特异性免疫反应。 他们认识到(外来的)蛋白质片段 - 肽结合在MHC分子的肽结合槽中。 这些肽MHC复合物在细胞内和细胞内产生,被T细胞识别。 因此,MHC限制性地表达来自细胞外源的(外源)肽的速率限制步骤是抗原呈递细胞对这些抗原的摄取以及递送至其中形成MHC-肽复合物的细胞内区室。 专业抗原呈递细胞如树突状细胞和巨噬细胞通过巨噬细胞增多和甘露糖受体介导的内吞作用占据抗原。 我们已经探索了其他非甘露糖基化抗原的甘露糖基化可导致甘露糖受体阳性细胞增强摄取和MHC限制性表达(片段)这种抗原的可能性。 使用甘露糖受体阳性培养的人树突状细胞作为抗原呈递细胞,我们发现与非甘露糖基化肽相比,抗原肽的甘露糖基化导致刺激MHC II类限制性肽特异性T细胞克隆的增强效力为300-10,000倍。 这些结果表明抗原的甘露糖基化导致选择性靶向和随后的树突状细胞的优异表达,其可能适用于例如疫苗设计。
    • 8. 发明申请
    • NEURONAL DATA PROCESSING NETWORK
    • 神经数据处理网络
    • WO1990010274A1
    • 1990-09-07
    • PCT/NL1990000018
    • 1990-02-20
    • RIJKSUNIVERSITEIT TE LEIDENWOLTERS, GezinusMURRE, Jacob, Marinus, JanPHAF, Rutger, Hans
    • RIJKSUNIVERSITEIT TE LEIDEN
    • G06F15/80
    • G06N3/04G06N99/005
    • A data processing module or neural network, comprising a plurality of nodes, as well as connections between said nodes, through which connections data weighted by a weighting factor can be transmitted between the nodes, said nodes having an activation value representative of the data received. There are provides at least three types of nodes; a first type (R) adapted to receive external data and at least two of which are present; a second type (V), one of which is always paired with a node of the first type; and a third type (A, E), at least one of which is present. Each node of the first type (R) is connected through a connection with a preferably positive weighting factor (up, low) to the associated node of the second type (V) and to the node of the third type (A, E). Each node of the second type (V) is connected through a connection with a preferably negative weighting factor (flat; cross; high) to the other nodes of the second type (V), to the nodes of the first type (R) not being paired therewith, and to the node of the third type (A, E). The node of the third type (A, E) is connected through connections with a preferably positive weighting factor (strange) to the nodes of the first type.
    • 包括多个节点的数据处理模块或神经网络以及所述节点之间的连接,通过该数据处理模块或神经网络可以在所述节点之间传送由加权因子加权的连接数据,所述节点具有表示接收到的数据的激活值。 提供至少三种类型的节点; 适于接收外部数据的第一类型(R),并且其中至少两个存在; 第二类型(V),其中之一总是与第一类型的节点配对; 和第三类型(A,E),其中至少一个存在。 第一类型(R)的每个节点通过具有优选正的加权因子(向上,向下)的连接连接到第二类型(V)的相关联节点并连接到第三类型(A,E)的节点。 第二类型(V)的每个节点通过具有优选负加权因子(平坦;交叉;高)到第二类型(V)的其他节点的连接连接到第一类型(R)的节点 与第三类型(A,E)配对。 第三类型(A,E)的节点通过具有优选正的加权因子(奇数)的连接连接到第一类型的节点。
    • 10. 发明申请
    • THE H-Y ANTIGEN
    • H-Y抗原
    • WO1997005168A1
    • 1997-02-13
    • PCT/NL1996000307
    • 1996-07-29
    • RIJKSUNIVERSITEIT TE LEIDENGOULMY, Els., A., J., M.HUNT, Donald, F.ENGELHARD, Victor, H.
    • RIJKSUNIVERSITEIT TE LEIDEN
    • C07K14/705
    • C07K14/705A61K38/00A61K39/00
    • H-Y is a transplantation antigen that can lead to rejection of HLA-matched male organ and bone marrow grafts by female recipients, and may play a role in pregnancy and spermatogenesis. However, the origin and function of H-Y antigens has eluded researchers for 40 years. We show that one human H-Y peptide antigen presented by HLA-B7 is an 11 residue peptide derived from SMCY, an evolutionarily conserved Y chromosomal protein. A homologous gene on the X chromosome, SMCX, differs by two residues in the same region. We also show a peptide antigen recognized by two HLA-A2.1 restricted T cell clones, which is also encoded by SMCY. The identification of H-Y offers prospects for improvements in transplantation outcome, prenatal diagnosis and fertilization strategies.
    • H-Y是一种移植抗原,可以导致女性接受者与HLA匹配的男性器官和骨髓移植物排斥,并可能在怀孕和精子发生中发挥作用。 然而,H-Y抗原的起源和功能已经使研究人员已经40年了。 我们显示HLA-B7提供的一种人H-Y肽抗原是衍生自SMCY(一种进化上保守的Y染色体蛋白)的11残基肽。 X染色体SMCX上的同源基因在同一区域有两个残基差异。 我们还显示由SMCY编码的两个HLA-A2.1受限T细胞克隆识别的肽抗原。 H-Y的鉴定提供了改善移植结果,产前诊断和受精策略的前景。