Multiscale modelling of T-cell development and selection in the thymus

Philippe August Robert (University of Oslo, Institute of Clinical Medicine)

Thursday 26th November 14:00-15:00 ZOOM (ID: 981 0015 2180)

Abstract

The thymus hosts the development of a type of adaptive immune cells, T-cells. From early thymic progenitors, these cells proliferate in synchronous waves. They recombine their DNA to each express a different immune receptor, the T-cell receptor (TCR). They further endure multiple quality checks via cellular interactions, ensuring they carry a functional but not harmful receptor, a process called ‘thymic selection’. The thymus is therefore responsible for producing a proper ‘repertoire’ of T-cells throughout life, reacting to any possible foreign attack while preserving the body by tolerating self-antigens. The thymus has been of striking interest for both immunologists and mathematical modellers due to its multiscale quantitative properties, bridging molecular binding into population dynamics and polyclonal repertoire specificity. Here, we introduce three levels of mathematical modelling strategies that helped to understand thymic function: i) the flexible dynamics of its highly dividing and dying cell populations, ii) how cellular interactions lead to a proper thymic selection, and iii) how TCR repertoire sequences are shaped. We discuss current challenges to accurately estimate in vivo cellular behaviour and ultimately reach next-generation multiscale models of T cell development

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