Translational Applications of New Insights into Immunoreceptor Signalling

免疫受体信号传导新见解的转化应用

• 批准号: MC_UU_00008/4
• 负责人: Simon Davis
• 金额: $ 185.91万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_UU_00008%2F4
• 关键词: Translational; Applications; New; Insights; into

The aim of the T-cell biology group, in its translational work, is to develop new antibodies for use as therapies in autoimmune diseases. To achieve this we are working towards an understanding of the biology of the leukocyte cell surface, and to apply this understanding to the development of new drug-like antibodies. Leukocytes are white blood cells that are involved in defending the body against infectious disease and foreign materials found in the blood and lymphatic circulatory systems. The surface of leukocytes is covered in protein molecules, some of which are receptors that interact with fragments of specific foreign proteins either from infectious agents or other foreign materials, such as allergens, or, as in the case of some autoimmune diseases, to self-antigens. When the receptors interact with their target molecules, we propose that they undergo a reorganization that causes them to trigger immune response pathways. If these pathways are triggered inappropriately, then autoimmune disease can develop. The process of receptor triggering by native ligands can be mimicked with antibodies, which means that, when we fully understand the process, we may be in a position to design new antibody-based receptor agonists for use in the treatment of autoimmune diseases.

T 细胞生物学小组的转化工作目标是开发新的抗体，用于治疗自身免疫性疾病。为了实现这一目标，我们正在努力了解白细胞表面的生物学，并将这种了解应用于新的药物样抗体的开发。白细胞是白细胞，参与保护身体免受传染病以及血液和淋巴循环系统中发现的异物的侵害。白细胞的表面覆盖着蛋白质分子，其中一些是与来自传染源或其他外来物质（例如过敏原）或自身抗原（如某些自身免疫性疾病）的特定外来蛋白质片段相互作用的受体。当受体与其目标分子相互作用时，我们认为它们会经历重组，从而触发免疫反应途径。如果这些途径​​被不适当地触发，那么就会出现自身免疫性疾病。天然配体触发受体的过程可以用抗体来模拟，这意味着，当我们完全了解该过程时，我们可能能够设计新的基于抗体的受体激动剂用于治疗自身免疫性疾病。

项目成果

Reconstitution of immune cell interactions in free-standing membranes.

独立膜中免疫细胞相互作用的重构。

• DOI: 10.1242/jcs.219709
• 发表时间: 2018-10-02
• 期刊: Journal of cell science
• 影响因子: 4
• 作者: Jenkins E;Santos AM;O'Brien-Ball C;Felce JH;Wilcock MJ;Hatherley D;Dustin ML;Davis SJ;Eggeling C;Sezgin E
• 通讯作者: Sezgin E

Monomeric TCRs drive T cell antigen recognition.

• DOI: 10.1038/s41590-018-0092-4
• 发表时间: 2018-05
• 期刊: Nature immunology
• 影响因子: 30.5
• 作者: Brameshuber M;Kellner F;Rossboth BK;Ta H;Alge K;Sevcsik E;Göhring J;Axmann M;Baumgart F;Gascoigne NRJ;Davis SJ;Stockinger H;Schütz GJ;Huppa JB
• 通讯作者: Huppa JB

Cytoskeletal actin dynamics shape a ramifying actin network underpinning immunological synapse formation.

• DOI: 10.1126/sciadv.1603032
• 发表时间: 2017-06
• 期刊: Science advances
• 影响因子: 13.6
• 作者: Fritzsche M;Fernandes RA;Chang VT;Colin-York H;Clausen MP;Felce JH;Galiani S;Erlenkämper C;Santos AM;Heddleston JM;Pedroza-Pacheco I;Waithe D;de la Serna JB;Lagerholm BC;Liu TL;Chew TL;Betzig E;Davis SJ;Eggeling C
• 通讯作者: Eggeling C

Single-cell measurements of two-dimensional binding affinity across cell contacts.

• DOI: 10.1016/j.bpj.2021.10.010
• 发表时间: 2021-11-16
• 期刊: Biophysical journal
• 影响因子: 3.4
• 作者: Chouliara M;Junghans V;Dam T;Santos AM;Davis SJ;Jönsson P
• 通讯作者: Jönsson P

A cell topography-based mechanism for ligand discrimination by the T cell receptor

• DOI: 10.1073/pnas.1817255116
• 发表时间: 2019-07-09
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Fernandes, Ricardo A.;Ganzinger, Kristina A.;Klenerman, David
• 通讯作者: Klenerman, David