Consequences of inter cellular molecular transfer in vitro and in vivo

体外和体内细胞间分子转移的后果

• 批准号: BB/J002011/1
• 负责人: Wilson Wong
• 金额: $ 54.06万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FJ002011%2F1
• 关键词: Consequences; inter; cellular; molecular; transfer

Cell to cell interaction within the immune system takes place within the immunological synapse. As a consequence, surface molecules can be exchanged. We will use an antibody-directed toxin approach to deplete recipient cells that have acquired donor MHC class II molecules (and vice versa) to study their contribution towards the rejection process in a mouse kidney allograft model. An anti donor MHC class II antibody will be used to direct a 'toxin' (gelonin) towards cells that express donor class II MHC molecules. If the donor (but not recipient) cells are resistant to the toxin, then only recipient (Multi drug resistant gene knockout mice which are toxin sensitive) cells that have acquired donor class II MHC molecules will be lysed. This will enable us to determine the relative contribution of this process to the alloresponse. We have synthesized this immunotoxin and demonstrated its effectiveness both in vitro and in vivo. In vitro experiments will also be performed to investigate the ability of the phenomenon to link the direct and indirect antigen presentation pathways. Understanding the consequences of MHC transfer will also have important implications in other fields where antigen presentation is involved, such as tumor immunology, vaccination, infection and auto-immune diseases.

免疫系统内的细胞与细胞的相互作用发生在免疫突触内。因此，表面分子可以交换。我们将使用抗体导向的毒素方法来消耗已获得供体MHC II类分子的受体细胞（反之亦然），以研究它们对小鼠肾同种异体移植模型中排斥过程的贡献。抗供体MHC II类抗体将用于将“毒素”（白树毒素）导向表达供体II类MHC分子的细胞。如果供体（而非受体）细胞对毒素具有抗性，则仅裂解获得供体II类MHC分子的受体（毒素敏感的多药抗性基因敲除小鼠）细胞。这将使我们能够确定这一过程对同种异体反应的相对贡献。我们已经合成了这种免疫毒素，并在体外和体内证明了其有效性。还将进行体外实验以研究该现象连接直接和间接抗原呈递途径的能力。了解MHC转移的后果也将在涉及抗原呈递的其他领域具有重要意义，例如肿瘤免疫学，疫苗接种，感染和自身免疫疾病。

项目成果

Immunotoxin in the Absence of P-Glycoprotein allows Selective Target Cell Killing in the Semi-Direct Antigen Presentation Pathway Following Organ Transplantation

缺乏 P-糖蛋白的免疫毒素可在器官移植后的半直接抗原呈递途径中选择性杀死靶细胞

• DOI: 10.1097/01.tp.0000542614.79078.e4
• 发表时间: 2018
• 期刊: Transplantation
• 影响因子: 6.2
• 作者: Meader L

Immunotoxin Against a Donor MHC Class II Molecule Induces Indefinite Survival of Murine Kidney Allografts.

• DOI: 10.1111/ajt.13584
• 发表时间: 2016-04
• 期刊: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
• 作者: Brown K;Nowocin AK;Meader L;Edwards LA;Smith RA;Wong W
• 通讯作者: Wong W

Characterizing the B-Cell and Humoral Response in Tertiary Lymphoid Organs in Kidney Allografts.

同种异体肾移植物中第三淋巴器官中 B 细胞和体液反应的特征。

• DOI: 10.6002/ect.2017.0261
• 发表时间: 2019
• 期刊: official journal of the Middle East Society for Organ Transplantation
• 作者: Nowocin AK