Physics (Internal)

Cellular heterogeneity and cooperativity shape decision-making in the immune system

This event is part of the Biophysics/Condensed Matter Seminar Series.

Abstract:
Cellular diversity, flexibility and robustness are crucial features of a
reliable immune system, in particular in the case of T lymphocytes
enforcing antigen discrimination. We combined computational modeling and
experimental measurements at the single cell level to demonstrate how
T-cells are highly variable in their sensitivity because of
heterogeneity of their protein expression. However, we also discovered
how cell-cell interactions proofread individual cell activation, correct
cellular noise and restore reliability of the immune response at the
system level. Specifically we tested how IL2-mediated quorum sensing
regulates rare sporadic activation while remaining vulnerable to large
scale ‘systematic errors’ and demonstrated the role of IL2 depletion by
regulatory T cells in the suppression of weakly activated effector
cells. Our work demonstrates that cell-cell dynamical feedback networks
are integrated over heterogeneous populations to achieve reliable
decision-making in the immune system.