Activation of plant immunity relies on recognition of pathogen effectors by several classes of plant resistance proteins. To discover the underlying molecular mechanisms of effector recognition by the Arabidopsis thaliana RECOGNITION OF PERONOSPORA PARASITICA1 (RPP1) resistance protein, we adopted an Agrobacterium tumefaciens-mediated transient protein expression system in tobacco (Nicotiana tabacum), which allowed us to perform coimmunoprecipitation experiments and mutational analyses. Herein, we demonstrate that RPP1 associates with its cognate effector ARABIDOPSIS THALIANA RECOGNIZED1 (ATR1) in a recognition-specific manner and that this association is a prerequisite step in the induction of the hypersensitive cell death response of host tissue. The leucine-rich repeat (LRR) domain of RPP1 mediates the interaction with ATR1, while the Toll/Interleukin1 Receptor (TIR) domain facilitates the induction of the hypersensitive cell death response. Additionally, we demonstrate that mutations in the TIR and nucleotide binding site domains, which exhibit loss of function for the induction of the hypersensitive response, are still able to associate with the effector in planta. Thus, our data suggest molecular epistasis between signaling activity of the TIR domain and the recognition function of the LRR and allow us to propose a model for ATR1 recognition by RPP1.