公开(公告)号：US20100279401A1

公开(公告)日：2010-11-04

申请号：US12527004

申请日：2005-07-07

申请人： Gregory G. Burrows ,  Yuan K. Chou ,  Arthur A. Vandenbark

发明人： Gregory G. Burrows ,  Yuan K. Chou ,  Arthur A. Vandenbark

IPC分类号： C12N5/16

CPC分类号： C12N5/0636 ,  C12N5/16 ,  C12N2503/00

摘要： The present invention provides T cell hybridomas and related compositions and assay systems for investigative, diagnostic, and therapeutic use in modulating T cell receptor (TCR)-mediated immune response. The T cell hybridomas of the invention are typically constructed by fusing a naïve or early central memory T cell isolated from a mammalian subject with an immortalizing fusion partner (e.g. mammalian lymphoid tumor cell) to yield clonal T cell hybrids. The resulting T cell hybridomas exhibit antigen (Ag)-specific proliferation responsiveness over a background level of proliferation of the hybridomas. These hybridomas are useful for screening, identifying, and characterizing T cell immune modulatory agents, for example recombinant T cell receptor ligands (RTLs) and other agents that can modulate TCR-mediated T cell immune responses. Ag-specific proliferative response profiles exhibited by the T cell hybridomas of the invention show sufficient amplitude, sensitivity and fidelity to distinguish and/or quantify the presence and/or activity of a test RTL or other test modulatory agent in screening and sensitivity assays employing the hybridomas. These and other aspects of the invention yield powerful tools and methods for developing and characterizing novel RTLs and other immune modulatory agents for use in treating immune disorders, including a wide range of autoimmune diseases, in mammals.

摘要翻译： 本发明提供了用于调节，诊断和治疗用途的T细胞杂交瘤以及用于调节T细胞受体（TCR）介导的免疫应答的相关组合物和测定系统。 本发明的T细胞杂交瘤通常通过将从哺乳动物受试者分离的初始或早期中央记忆T细胞与永生化融合配偶体（例如哺乳动物淋巴样肿瘤细胞）融合而构建，以产生克隆T细胞杂交体。 所得的T细胞杂交瘤在杂交瘤的增殖的背景水平上表现出抗原（Ag）特异性增殖反应性。 这些杂交瘤可用于筛选，鉴定和表征T细胞免疫调节剂，例如重组T细胞受体配体（RTL）和可调节TCR介导的T细胞免疫应答的其它试剂。 本发明的T细胞杂交瘤显示的Ag特异性增殖反应谱在筛选和敏感性测定中显示足够的幅度，灵敏度和保真度以区分和/或定量测试RTL或其他测试调节剂的存在和/或活性 杂交瘤。 本发明的这些和其它方面产生用于开发和表征用于哺乳动物治疗免疫疾病（包括广泛的自身免疫性疾病）的新型RTL和其它免疫调节剂的有力工具和方法。