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Machine learning analysis of the T cell receptor repertoire identifies sequence features that predict self-reactivity

bioRxiv, ISSN: 2692-8205
2022
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    Citations
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Metric Options:   Counts1 Year3 Year

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  • Citations
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    • Citation Indexes
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      • CrossRef
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  • Mentions
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    • News Mentions
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      • 1

Most Recent News

Machine learning analysis of the T cell receptor repertoire identifies sequence features that predict self-reactivity (Updated March 22, 2023)

2023 APR 05 (NewsRx) -- By a News Reporter-Staff News Editor at Health & Medicine Daily -- According to news reporting based on a preprint

Article Description

The T cell receptor (TCR) determines the specificity and affinity for both foreign and self-peptides presented by MHC. It is established that self-pMHC reactivity impacts T cell function, but it has been challenging to identify TCR sequence features that predict T cell fate. To discern patterns distinguishing TCRs from naïve CD4 T cells with low versus high self-pMHC reactivity, we used data from 42 mice to train a machine learning (ML) algorithm that predicts self-reactivity directly from TCRβ sequences. This approach revealed that n-nucleotide additions and acidic amino acids weaken self-reactivity. We tested our ML predictions of TCRβ sequence self-reactivity using retrogenic mice. Extrapolating our analyses to independent datasets, we found high predicted self-reactivity for regulatory CD4 T cells and low predicted self-reactivity for T cells responding to chronic infection. Our analyses suggest a potential trade-off between repertoire diversity and self-reactivity intrinsic to the architecture of a TCR repertoire.

Bibliographic Details

Johannes Textor; Franka Buytenhuijs; Shabaz Sultan; Inge M.N. Wortel; Dakota Rogers; Judith N. Mandl; Ève Mallet Gauthier; Heather J. Melichar; Kathrin Kalies; Anke Fähnrich; René Pagel; Jürgen Westermann

Cold Spring Harbor Laboratory

Biochemistry, Genetics and Molecular Biology; Agricultural and Biological Sciences; Immunology and Microbiology; Neuroscience; Pharmacology, Toxicology and Pharmaceutics

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