Analysis and simulations of Bcl10 self-assembly and degradation in activated T cells*

The adaptive immune system serves as a potent and highly specific defense mechanism against pathogens. A component of this system, the effector T cell, provides rapid pathogen-clearing responses upon detecting pathogen-associated signals. Stimulation of the T cell receptor leads to a signaling cascade resulting in pathogen eradication. Bcl10, a key regulatory protein in this cascade, rapidly assembles into filaments that form the core of the signal transduction machinery; simultaneously, Bcl10 is targeted for slow degradation to ensure tight control of immune activation. Despite the importance of Bcl10 for an effective immune response, the mechanisms and timescales of its assembly and degradation are poorly understood. Here, we will provide insights into Bcl10 filament formation and degradation via image analysis and Monte Carlo simulations. Using image-based bootstrapping, we show that Bcl10 preferentially colocalizes with autophagosomes and that the spatial organization of this complex is significant for immune function. Using stochastic Monte Carlo simulations, we shed light on key Bcl10 filament dynamics, including nucleation, growth, and degradation. Together, these data provide key insights into important mechanism that regulate adaptive immunity.