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. 2021 Oct 8;12:748768. doi: 10.3389/fimmu.2021.748768

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Copyright © 2021 Liu, Qi, Milner, Lu and Cao

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Fold-change detection in the incoherent feedforward loop (IFFL) reveals the impact of antigen presentation dynamics. (A) IFFL provides fold-change detection. Two inputs (gray and dashed red lines) of the same fold-change yield identical outputs, despite different baselines. (B) Antigen stimulus dynamics influences CAR-T cell response. Four patterns of antigen stimulus with equivalent area under the curve (AUC) were explored. (1) Constant appearance; (2) high but transient appearance; (3) linear appearance; and (4) exponential appearance of antigen (input X) yielded responses (output Z) with diverse amplitude, duration, and cumulative strength (AUC) profiles.