T-cell Receptor Is a Threshold Detector: Sub- and Supra-Threshold Stochastic Resonance in TCR-MHC Clusters on the Cell Surface

Entropy (Basel). 2022 Mar 10;24(3):389. doi: 10.3390/e24030389.

Abstract

Stochastic resonance in clusters of major histocompatibility molecules is extended by a more detailed description of adaptive thresholding and by applying the notion of suprathreshold stochastic resonance as a stochastically quantizing encoder of transmembrane signaling downstream of major histocompatibility molecules and T-cell receptors on the side of presenting and recognizing cells, respectively. The adaptive nature of thresholding is partly explained by a mirroring of the noncognate-cognate dichotomy shown by the T-cell receptor structure and the kinetic-segregation model of the onset of T-cell receptor triggering. Membrane clusters of major histocompatibility molecules and T-cell receptors on their host cells are envisioned as places of the temporal encoding of downstream signals via the suprathreshold stochastic resonance process. The ways of optimization of molecular prostheses, such as chimeric antigen receptors against cancer in transmembrane signaling, are suggested in the framework of suprathreshold stochastic resonance. The analogy between Förster resonance energy transfer and suprathreshold stochastic resonance for information transfer is also discussed. The overlap integral for energy transfer parallels the mutual information transferred by suprathreshold stochastic resonance.

Keywords: CD8/CD4; Förster resonance energy transfer (FRET); MHCI/MHCII; TCR; chimeric antigen receptor (CAR) optimization; correlation; distributed signal detection; mutual information; noncognate–cognate discrimination; pattern recognition.

Publication types

  • Review