A built-in brake for plant immunity: Resistance (R) protein-mediated immunity is fine-tuned by R gene analogs.

Potato late blight caused by Phytophthora infestans threatens global food security. Unlike the fact that most race-specific resistance to P. infestans (Rpi) genes is rapidly overcome by evolving pathogen populations, the R8 gene from Solanum demissum has conferred durable, quantitative resistance for nearly a century despite encoding a canonical coiled-coil-type nucleotide-binding, leucine-rich repeat (NLR) protein. We identified specific R8 gene analogs that act as negative modulators of R8-mediated immunity. These R8 gene analogs lack independent resistance functions but perturb the recognition of avirulence effector Avr8 by R8 and interfere with oligomerization and plasma membrane association of NRC2, a helper NLR essential for the R8 signaling pathway. Stable overexpression of such RGAs effectively compromises R8-mediated resistance in both potato and Nicotiana benthamiana. We propose that this endogenous regulation balances the intensity of R8-mediated immunity, likely reducing selection pressure on the pathogen population and prolonging resistance durability. Our findings reveal a regulatory layer where genetically linked RGAs control resistance (R) protein-mediated immunity, providing a conceptual framework for durable resistance breeding.