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. 2025 Aug 22;11(34):eadw3995. doi: 10.1126/sciadv.adw3995

Fig. 5. Reversibility of the TCR signaling Boolean network.

Fig. 5.

(A) TCR signaling Boolean network. (B) Phenotype landscape under nominal conditions. Half of the states produce the P1 phenotype, half of the remaining states produce the P2 phenotype, and the rest primarily produce the P3 phenotype. Other phenotypes have relatively small basin sizes. (C) Altered phenotype landscape under LoF of Gab2 and GoF of ZAP70. States from the basins of P2 and P3 now produce the AP1 phenotype, which is equivalent to P1. Other phenotypes are also distorted. (D) Controlled phenotype landscape under suppression of LAT. The three major phenotypes from the nominal phenotype landscape, P1, P2, and P3, are restored as CP1, CP2, and CP3. (E) Mechanism causing the distorted phenotype landscape. Because of the alterations, the JNK/Jun pathway and Ras/MEK/ERK pathway are dysregulated, leading to abnormal activation of AP1 and CRE. (F) Mechanism restoring the nominal phenotype landscape. Through suppression of LAT, the JNK/Jun pathway and Ras/MEK/ERK pathway are properly regulated, restoring normal phenotype landscape dynamics. NF-κB, nuclear factor κB; IκB, inhibitor of nuclear factor B.