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1.发明申请Antigens Targeted by Pathogenic Al4 T Cells in Type 1 Diabetes and Uses Thereof 有权1型糖尿病中致病性Al4T细胞靶向的抗原及其用途公开(公告)号：US20100009923A1
公开(公告)日：2010-01-14
申请号：US11658457
申请日：2005-07-26
CPC分类号： C07K14/47
摘要： Provided are oligopeptide antigens to A14-like T cells, and mouse proteins comprising those antigens. The oligopeptide antigens comprise the amino acid sequence XX(I/D/F/L)ENY(I/L)(E/W/Y)(L/M) or VMLENYTHL. Additionally provided are methods for treating a mammal having or at risk for type 1 diabetes using these antigens, or compounds which reduce or eliminate expression of these antigens. Kits comprising these antigens, and methods for determining whether a mammal is at risk for or has type 1 diabetes are also provided.
摘要翻译： 提供对A14样T细胞的寡肽抗原，以及包含那些抗原的小鼠蛋白质。 寡肽抗原包含氨基酸序列XX（I / D / F / L）ENY（I / L）（E / W / Y）（L / M）或VMLENYTHL。 另外提供了使用这些抗原治疗患有或具有1型糖尿病风险的哺乳动物的方法，或减少或消除这些抗原表达的化合物。 还提供了包含这些抗原的试剂盒，以及用于确定哺乳动物是否处于或具有1型糖尿病风险的方法。
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2.发明授权Antigens targeted by pathogenic AI4 T cells in type 1 diabetes and uses thereof 有权1型糖尿病中致病性AI4 T细胞靶向的抗原及其用途公开(公告)号：US08318670B2
公开(公告)日：2012-11-27
申请号：US11658457
申请日：2005-07-26
CPC分类号： C07K14/47
摘要： Provided are oligopeptide antigens to AI4-like T cells, and mouse proteins comprising those antigens. The oligopeptide antigens comprise the amino acid sequence XX(I/D/F/L)ENY(I/L)(E/W/Y)(L/M) or VMLENYTHL. Additionally provided are methods for treating a mammal having or at risk for type 1 diabetes using these antigens, or compounds which reduce or eliminate expression of these antigens. Kits comprising these antigens, and methods for determining whether a mammal is at risk for or has type 1 diabetes are also provided.
摘要翻译： 提供对于类似Aβ的T细胞的寡肽抗原，以及包含这些抗原的小鼠蛋白质。 寡肽抗原包含氨基酸序列XX（I / D / F / L）ENY（I / L）（E / W / Y）（L / M）或VMLENYTHL。 另外提供了使用这些抗原治疗患有或具有1型糖尿病风险的哺乳动物的方法，或减少或消除这些抗原表达的化合物。 还提供了包含这些抗原的试剂盒，以及用于确定哺乳动物是否处于或已经具有1型糖尿病的风险的方法。
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3.发明申请Antigens Targeted by Pathogenic T Cells in Type 1 Diabetes and Uses Thereof 审中-公开1型糖尿病中致病性T细胞靶向的抗原及其用途公开(公告)号：US20090137485A1
公开(公告)日：2009-05-28
申请号：US11886482
申请日：2006-03-09
CPC分类号： A61K39/0008 , A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2227/105 , A01K2267/0362 , A61K38/00 , C07K14/70539
摘要： Provided are polypeptides that are capable of binding a human HLA-A2 MHC class I molecule. Kits comprising these polypeptides in a container are also provided. Further provided are methods for determining whether a mammal is at risk for or has type 1 diabetes. Additionally provided are methods of preventing a CD8+ T cell that is cytotoxic to pancreatic islet β-cells from destroying a β-cell. Methods of treating a mammal that is at risk for type 1 diabetes are also provided, as are methods of treating a mammal that has type 1 diabetes.
摘要翻译： 提供能够结合人HLA-A2 MHC I类分子的多肽。 还提供了在容器中包含这些多肽的试剂盒。 还提供了用于确定哺乳动物是否处于或具有1型糖尿病的风险的方法。 另外提供了防止对胰岛β细胞具有细胞毒性的CD8 + T细胞破坏β细胞的方法。 还提供了治疗1型糖尿病风险的哺乳动物的方法，以及治疗具有1型糖尿病的哺乳动物的方法。
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4.发明授权Antigens targeted by prevalent pathogennic T cells in type 1 diabetes and uses thereof 有权1型糖尿病中流行的病原性T细胞靶向的抗原及其用途公开(公告)号：US08758767B2
公开(公告)日：2014-06-24
申请号：US10557273
申请日：2004-05-20
申请人： Teresa P. DiLorenzo , Anne M. Evans , Donald F. Hunt , Scott M. Lieberman , Stanley G. Nathenson , Pere Santamaria , Jeffrey Shabanowitz
发明人： Teresa P. DiLorenzo , Anne M. Evans , Donald F. Hunt , Scott M. Lieberman , Stanley G. Nathenson , Pere Santamaria , Jeffrey Shabanowitz
IPC分类号： A61K39/00 , A61K39/385
CPC分类号： C07K14/4711
摘要： The present invention is based on the identification of a predominant ligand of CD8+ T cells that are responsible for type 1 diabetes. That ligand is islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP). Several CD8+ T cell-binding peptides from IGRP are identified, including the peptide comprising amino acids 206-214 of the IGRP sequence, which has high avidity to the most prevalent T cell receptor of pathogenic CD8+ T cells in autoimmune diabetes. The invention thus provides oligopeptide and polypeptide compositions comprising YLKTN(A/I/L/V)FL (SEQ ID NO:3), FLWSVFWLI (SEQ ID NO:4), (T/A)YY(G/T)FLNFM (SEQ ID NO:5), LR(L/V)(F/L)(G/N)IDLL (SEQ ID NO:6), KWCANPDWI (SEQ ID NO:7), and SFCKSASIP (SEQ ID NO:8). Also provided are oligopeptide compositions 8-10 amino acids in length and completely homologous with a mammalian IGRP, where the oligopeptide is capable of binding a human MHC class I molecule. Additionally, various methods of treating a mammal using the above compositions are provided, where the mammal is at risk for or has type 1 diabetes. Also provided are methods of preventing a CD8+ T cell that is cytotoxic to pancreatic islet β-cells from destroying a mammalian β-cell, where the methods also use the above compositions. Further provided are methods for determining whether a mammal is at risk for or has type 1 diabetes, where the methods use the above compositions.
摘要翻译： 本发明基于负责1型糖尿病的CD8 + T细胞的主要配体的鉴定。 该配体是胰岛特异性葡萄糖-6-磷酸酶催化亚单位相关蛋白（IGRP）。 鉴定了来自IGRP的几种CD8 + T细胞结合肽，包括含有IGRP序列的氨基酸206-214的肽，其对自身免疫性糖尿病中病原性CD8 + T细胞最流行的T细胞受体具有高亲合力。 因此，本发明提供包含YLKTN（A / I / L / V）FL（SEQ ID NO：3），FLWSVFWLI（SEQ ID NO：4），（T / A）YY（G / T）FLNFM SEQ ID NO：5），LR（L / V）（F / L）（G / N）IDLL（SEQ ID NO：6），KWCANPDWI（SEQ ID NO：7）和SFCKSASIP（SEQ ID NO：8） 。 还提供了长度为8-10个氨基酸且与哺乳动物IGRP完全同源的寡肽组合物，其中寡肽能够结合人MHC I类分子。 此外，提供使用上述组合物治疗哺乳动物的各种方法，其中哺乳动物处于或具有1型糖尿病的风险。 还提供了防止对胰岛细胞具有细胞毒性的CD8 + T细胞破坏哺乳动物和细胞的方法，其中所述方法也使用上述组合物。 还提供了用于确定哺乳动物是否处于或患有1型糖尿病的风险的方法，其中所述方法使用上述组合物。
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5.发明申请Antigens Targeted by Prevalent Pathogennic T Cells in Type 1 Diabetes and Uses Thereof 有权1型糖尿病中普遍的病原性T细胞靶向的抗原及其用途公开(公告)号：US20080153112A1
公开(公告)日：2008-06-26
申请号：US10557273
申请日：2004-05-20
申请人： Teresa P. DiLorenzo , Anne M. Evans , Donald F. Hunt , Scott M. Lieberman , Stanley G. Nathenson , Pere Santamaria , Jeffrey Shabanowitz
发明人： Teresa P. DiLorenzo , Anne M. Evans , Donald F. Hunt , Scott M. Lieberman , Stanley G. Nathenson , Pere Santamaria , Jeffrey Shabanowitz
IPC分类号： A61K31/711 , A61K38/08 , A61P3/10 , C07H21/02 , C07H21/04 , C07K14/00 , C07K7/00 , C12N5/06 , G01N33/567
CPC分类号： C07K14/4711
摘要： The present invention is based on the identification of a predominant ligand of CD8+ T cells that are responsible eq for type 1 diabetes. That ligand is islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP). Several CD8+ T cell-binding peptides from IGRP are identified, including the peptide comprising amino acids 206-214 of the IGRP sequence, which has high avidity to the most prevalent T cell receptor of pathogenic CD8+ T cells in autoimmune diabetes. The invention thus provides oligopeptide and polypeptide compositions comprising YLKTN/A/I/L/V)FL, FLWSVFWLI, (T/A)YY/G/T)FLNFM, LR(LV)(F/L)(G/N)IDLL, KWCANPDWI, and SFCKSASIP. Also provided are oligopeptide compositions 8-10 amino acids in length and completely homologous with a mammalian IGRP, where the oligopeptide is capable of binding a human MHC class I molecule. Additionally, various methods of treating a mammal using the above compositions are provided, where the mammal is at risk for or has type 1 diabetes. Also provided are methods of preventing a CD8+ T cell that is cytotoxic to pancreatic islet β-cells from destroying a mammalian β-cell, where the methods also use the above compositions. Further provided are methods for determining whether a mammal is at risk for or has type 1 diabetes, where the methods use the above compositions.
摘要翻译： 本发明基于鉴定负责1型糖尿病的CD8 + T细胞的主要配体。 该配体是胰岛特异性葡萄糖-6-磷酸酶催化亚单位相关蛋白（IGRP）。 鉴定了来自IGRP的几种CD8 + T细胞结合肽，包括含有IGRP序列的氨基酸206-214的肽，其对自身免疫性糖尿病中病原性CD8 + T细胞最流行的T细胞受体具有高亲合力。 本发明提供包含YLKTN / A / I / L / V）FL，FLWSVFWLI，（T / A）YY / G / T）FLNFM，LR（LV）（F / L）（G / N）的寡肽和多肽组合物 IDLL，KWCANPDWI和SFCKSASIP。 还提供了长度为8-10个氨基酸且与哺乳动物IGRP完全同源的寡肽组合物，其中寡肽能够结合人MHC I类分子。 此外，提供使用上述组合物治疗哺乳动物的各种方法，其中哺乳动物处于或具有1型糖尿病的风险。 还提供了防止对胰岛β细胞具有细胞毒性的CD8 + T细胞破坏哺乳动物β细胞的方法，其中该方法也使用上述组合物。 还提供了用于确定哺乳动物是否处于或患有1型糖尿病的风险的方法，其中所述方法使用上述组合物。
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