Superantigens in Epstein-Barr Virus Pathology

EB 病毒病理学中的超级抗原

• 批准号: 6642963
• 负责人: CHRISTOPHER T RANKIN
• 金额: $ 10万
• 依托单位: MACROGENICS, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-06 至 2004-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6642963
• 关键词: Epstein Barr virus; T lymphocyte; carcinogenesis inhibitor; clinical research; human subject; immunologic substance development /preparation; laboratory mouse; leukocyte activation /transformation; lymphoma; monoclonal antibody; passive immunization; superantigens; virus envelope; virus related neoplasm /cancer

DESCRIPTION (provided by applicant): Superantigens (SAG) are believed to contribute to the pathogenesis of certain infectious agents by activating a broad subset of primary T-cells. Through association with MHC class II molecules outside of the peptide recognition cleft, the SAG is able to bind and activate T-cells expressing a particular T-cell receptor (TCR) beta chain variable gene. Recent experiments have identified a SAG, encoded by the human endogenous retrovirus K18 env (HK18 env) gene, which is transcriptionally activated following infection with the Epstein-Barr virus (EBV). EBV is a ubiquitous, B-cell tropic herpesvirus, which has been identified as a causative agent for infectious mononucleosis (IM), a self-limiting lymphoproliferative disorder characterized by mononuclear leukocytosis. The association of EBV and a SAG activity provides an attractive hypothesis for the mechanism of EBV related T-cell proliferation. However, the exact role of the SAG in EBV infection and pathology is not currently known. The goal of this phase I application is to evaluate the role of the recently identified SAG molecule, HERV-K18 Env, in EBV infection and pathology. Our working hypothesis is that SAG activated T-cells supply an essential component necessary for the development of EBV associated B-cell lymphomas. Thus, blocking T-cell activation by the SAG could effectively prevent the development of EBV tumors. If this hypothesis is correct, these studies will provide a basis for phase II studies in primate models of EBV infection, in order to examine the potential for anti-SAG antibodies as preventative or therapeutic agents against EBV related disease.

描述（由申请人提供）：超抗原（SAG）被认为通过激活初级 T 细胞的广泛子集而促进某些感染因子的发病机制。通过与肽识别裂隙外的 MHC II 类分子结合，SAG 能够结合并激活表达特定 T 细胞受体 (TCR) β 链可变基因的 T 细胞。最近的实验发现了由人内源性逆转录病毒 K18 env (HK18 env) 基因编码的 SAG，该基因在感染 Epstein-Barr 病毒 (EBV) 后转录被激活。 EBV 是一种普遍存在的 B 细胞嗜性疱疹病毒，已被确定为传染性单核细胞增多症 (IM) 的病原体，而传染性单核细胞增多症是一种以单核白细胞增多为特征的自限性淋巴细胞增殖性疾病。 EBV 和 SAG 活性的关联为 EBV 相关 T 细胞增殖的机制提供了一个有吸引力的假设。然而，SAG 在 EBV 感染和病理学中的确切作用目前尚不清楚。该一期应用的目标是评估最近发现的 SAG 分子 HERV-K18 Env 在 EBV 感染和病理学中的作用。 我们的工作假设是，SAG 激活的 T 细胞提供了 EBV 相关 B 细胞淋巴瘤发展所必需的重要成分。因此，通过 SAG 阻断 T 细胞激活可以有效预防 EBV 肿瘤的发展。如果这一假设正确，这些研究将为 EBV 感染灵长类动物模型的 II 期研究提供基础，以检验抗 SAG 抗体作为 EBV 相关疾病的预防或治疗剂的潜力。