Broad cross-reactivity of the T-cell repertoire achieves specific and sufficiently rapid target searching

DOI10.1016/J.JTBI.2019.01.025zbMATH Open1411.92069arXiv1712.04633OpenAlexW2963150450WikidataQ91279338 ScholiaQ91279338MaRDI QIDQ1739293FDOQ1739293

Authors: Jin Xu, Junghyo Jo 

Publication date: 26 April 2019

Published in: Journal of Theoretical Biology (Search for Journal in Brave)

Abstract: The immune system must recognize countless pathogens throughout life. How does this system organize the finite but effective repertoire of receptors? This finite set of receptors must inevitably be cross-reactive to multiple pathogens while retaining high specificity to different pathogens. In this study, we computationally examined the cross-reactivity of T-cell receptors and peptides derived from infectious diseases based on the pairwise binding energy of their amino acid sequences. We found that T-cell receptors have diverse amino acid compositions, leading to a broad spectrum of cross-reactivity in peptide binding. High/low cross-reactive T-cell receptors have more/less strongly interacting amino acids. Then, we investigated the target searching time of the natural T-cell repertoire and compared the target searching time between the high and low cross-reactive T-cell repertoires. According to our computational results, the natural T-cell repertoire is specific and sufficiently rapid in searching for certain targets. High cross-reactive and non-specific T cells require more time to unbind from incorrect targets, while low cross-reactive T cell receptors require more time to search for the correct targets. Our computational platform, which is based on molecular sequences and their pairwise binding energy, could be useful in further explorations of immunological recognition.

Full work available at URL: https://arxiv.org/abs/1712.04633

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zbMATH Keywords

molecular recognitiontarget searchingcross-reactivityadaptive immunity

Mathematics Subject Classification ID

Biochemistry, molecular biology (92C40) Physiology (general) (92C30)

Cites Work

• The influence of T cell development on pathogen specificity and autoreactivity
• Binding of transcription factors adapts to resolve information-energy tradeoff
• Random-energy model: an exactly solvable model of disordered systems
• Explaining high alloreactivity as a quantitative consequence of affinity-driven thymocyte selection

Cited In (1)

• T-cell receptor optimization with reinforcement learning and mutation polices for precision immunotherapy

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