Signal length not strength guides t cell fate

Access through your institution Buy or subscribe During positive selection in the thymus, double-positive (DP) thymocytes expressing both CD4 and CD8 coreceptors develop into either MHC

class II-restricted CD4+ T cells with helper function or MHC class I-restricted CD8+ T cells with cytotoxic function, but it has been unclear how coreceptor expression and T cell function

are coordinated. T cell receptor (TCR) ‘signal strength’ models propose that strong signals through CD4–TCR induce a helper-lineage fate, whereas weak signals through CD8–TCR induce a

cytotoxic lineage fate. ‘Kinetic signalling’ models propose that longer-duration CD4–TCR signals versus shorter-duration CD8–TCR signals determine helper versus cytotoxic fates. Shinzawa et

al. now report the generation of FlipFlop mice, in which the coreceptor proteins encoded by the _Cd4_ and _Cd8_ loci are reversed, shedding light on the importance of TCR signal length

versus strength in T cell lineage fate. The MHC class specificity of T cells was unaffected in FlipFlop mice, with the MHC class I-restricted OT-I TCR selecting for CD8+ T cells and the MHC

class II-restricted OT-II TCR selecting for CD4+ T cells, but with a reversal of helper and cytotoxic phenotypes in FlipFlop mice. Thus, signalling through the same TCR and same coreceptor

can lead to opposite lineage fates dependent on the gene locus of coreceptor expression — the _Cd4_ locus promotes helper lineage fate whereas the _Cd8_ locus promotes cytotoxic lineage

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ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES ORIGINAL ARTICLE * Shinzawa, M. et al. Reversal of the T cell immune

system reveals the molecular basis for T cell lineage fate determination in the thymus. _Nat. Immunol._ https://doi.org/10.1038/s41590-022-01187-1 (2022) Article  PubMed  PubMed Central 

Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Nature Reviews Immunology http://www.nature.com/nri/ Kirsty Minton Authors * Kirsty Minton View author

publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Kirsty Minton. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS

ARTICLE CITE THIS ARTICLE Minton, K. Signal length not strength guides T cell fate. _Nat Rev Immunol_ 22, 407 (2022). https://doi.org/10.1038/s41577-022-00736-x Download citation *

Published: 16 May 2022 * Issue Date: July 2022 * DOI: https://doi.org/10.1038/s41577-022-00736-x SHARE THIS ARTICLE Anyone you share the following link with will be able to read this

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