Understanding how antigenic origin dictates antigenic fate and T-cell responses

Dr Ed Roberts & Prof Sara Zanivan

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Labs: Immune Priming and the Tumour Microenvironment and Tumour Microenvironment and Proteomics
Duration: 4 years, starting Oct 2023
Closing Date: 6th January 2023

Project Description

The immune response must both maintain tolerance to self-antigens while initiating robust T-cell responses against diverse challenges including viruses and tumours and these tasks must be completed simultaneously. This is complicated by the fact that T-cell responses are initiated in the lymph node which is distal to the site of antigen origin. The immune system must, therefore, solve an information transfer problem conveying contextual cues alongside antigens to the lymph node. This can be carried out by conventional dendritic cells (cDC) which sense associated signals when engulfing proteins and this defines how they process and the context in which they present antigen. However, part of these processes are carried out by lymph node resident cDC which have no contact with the periphery. This project seeks to understand how an antigen's origin determines its dispersal and ultimate fate within the lymph node.

We have previously demonstrated that antigen processing and transfer is altered based on the presence of pathogen associated molecular patterns. Using both in vitro and in vivo models you will dissect how signals associated with infection or tumour development alter phagosomal maturation and how this interacts with antigen transfer to lymph node resident cDC. This will subsequently lead to attempts to manipulate antigenic fate in the context of autoimmunity and tumour development to alter T-cell outcomes. The project will involve the use of a variety of techniques including molecular biology, tissue culture, proteomics, in vivo models, flow cytometry and advanced light microscopy.

For informal enquiries or further details on the project, please contact Dr Ed Roberts (ed.roberts@glasgow.ac.uk).

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Publications

Ruhland MK, Roberts EW, Cai E, Mujal AM, Marchuk K, Beppler C, Nam D, Serwas NK, Binnewies M, Krummel MF. Visualizing Synaptic Transfer of Tumor Antigens among Dendritic Cells. Cancer Cell. 2020 Jun 8;37(6):786-799.e5. doi: 10.1016/j.ccell.2020.05.002.

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