Single Cells Signal Non-self from Self via ‘XOR’ and ‘NOT EQUALS’ Logic in a Dimer of Dimers
An, R., & Prakash, M. (2024). Single Cells Signal Non-self from Self via'XOR'and'NOT EQUALS'Logic in a Dimer of Dimers. bioRxiv, 2024-10.
Link: https://www.biorxiv.org/content/10.1101/2024.10.01.616003v1.abstract
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The ciliate Tetrahymena thermophila’s seven mating types are defined by unique receptor-ligand pairs (Mta/Mtb). While Mta and Mtb are known to participate in a mating signal complex, how they distinguish between oneself and six non-self cell types remains unknown. AlphaFold3 predictions reveal Mta/Mtb as large glycoproteins likely derived from ancient, unisexual, intercellular adhesion molecules. Since homologous binary-type systems perform XOR by switching mtA expression, we show spectrum (n) types naturally extend XOR to multi-bit NOT EQUALS operations via differential affinities of Mta/Mtb dimers. We model kinetics begetting the ‘n + 1th’ type, demonstrating self-inhibition by trans-homophilic Mtb-Mtb. A computational approach reconciles recent and classical evidence for mating exclusivity, including selfing failures (same type mating). Binding kinetics enables fast, robust intercellular computation across an intermembrane mating space. Thus, Mta/Mtb families are a model system allowing us to derive a ‘calculus’ of antigenic variation and inspire synthetic designs of XOR logic underlying self/non-self recognition.
