The order and logic of CD4 versus CD8 lineage choice and differentiation in mouse thymus

Mohammad M. Karimi, Ya Guo, Xiaokai Cui, Husayn A. Pallikonda, Veronika Horková, Yi-Fang Wang, Sara Ruiz Gil, Gustavo Rodriguez-Esteban, Irene Robles-Rebollo, Ludovica Bruno, Radina Georgieva, Bhavik Patel, James Elliott, Marian H. Dore, Danielle Dauphars, Michael S. Krangel, Boris Lenhard, Holger Heyn, Amanda G. Fisher, Ondřej Štěpánek and Matthias Merkenschlager ()
Additional contact information
Mohammad M. Karimi: Imperial College London
Ya Guo: Imperial College London
Xiaokai Cui: Imperial College London
Husayn A. Pallikonda: Imperial College London
Veronika Horková: Institute of Molecular Genetics of the Czech Academy of Sciences
Yi-Fang Wang: Imperial College London
Sara Ruiz Gil: The Barcelona Institute of Science and Technology (BIST)
Gustavo Rodriguez-Esteban: The Barcelona Institute of Science and Technology (BIST)
Irene Robles-Rebollo: Imperial College London
Ludovica Bruno: Imperial College London
Radina Georgieva: Imperial College London
Bhavik Patel: Imperial College London
James Elliott: Imperial College London
Marian H. Dore: Imperial College London
Danielle Dauphars: Duke University Medical Center
Michael S. Krangel: Duke University Medical Center
Boris Lenhard: Imperial College London
Holger Heyn: The Barcelona Institute of Science and Technology (BIST)
Amanda G. Fisher: Imperial College London
Ondřej Štěpánek: Institute of Molecular Genetics of the Czech Academy of Sciences
Matthias Merkenschlager: Imperial College London

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract CD4 and CD8 mark helper and cytotoxic T cell lineages, respectively, and serve as coreceptors for MHC-restricted TCR recognition. How coreceptor expression is matched with TCR specificity is central to understanding CD4/CD8 lineage choice, but visualising coreceptor gene activity in individual selection intermediates has been technically challenging. It therefore remains unclear whether the sequence of coreceptor gene expression in selection intermediates follows a stereotypic pattern, or is responsive to signaling. Here we use single cell RNA sequencing (scRNA-seq) to classify mouse thymocyte selection intermediates by coreceptor gene expression. In the unperturbed thymus, Cd4+Cd8a- selection intermediates appear before Cd4-Cd8a+ selection intermediates, but the timing of these subsets is flexible according to the strength of TCR signals. Our data show that selection intermediates discriminate MHC class prior to the loss of coreceptor expression and suggest a model where signal strength informs the timing of coreceptor gene activity and ultimately CD4/CD8 lineage choice.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20306-w

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DOI: 10.1038/s41467-020-20306-w

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