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28 March 2024
 
  » pubmed » pmid10761920

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The duration of antigen receptor signalling determines CD4+ versus CD8+ T-cell lineage fate
K Yasutomo ; C Doyle ; L Miele ; C Fuchs ; R N Germain ;
Date 30 Mar 2000
Journal Nature, 404 (6777), 506-10
AbstractSignals elicited by binding of the T-cell antigen receptor and the CD4/CD8 co-receptor to major histocompatibility complex (MHC) molecules control the generation of CD4+ (helper) or CD8+ (cytotoxic) T cells from thymic precursors that initially express both co-receptor proteins. These precursors have unique, clonally distributed T-cell receptors with unpredictable specificity for the self-MHC molecules involved in this differentiation process. However, the mature T cells that emerge express only the CD4 (MHC class II-binding) or CD8 (MHC class I-binding) co-receptor that complements the MHC class-specificity of the T-cell receptor. How this matching of co-receptor-defined lineage and T-cell-receptor specificity is achieved remains unknown, as does whether signalling by the T-cell receptors, co-receptors and/or general cell-fate regulators such as Notch-1 contributes to initial lineage choice, to subsequent differentiation processes or to both. Here we show that the CD4 versus CD8 lineage fate of immature thymocytes is controlled by the co-receptor-influenced duration of initial T-cell receptor-dependent signalling. Notch-1 does not appear to be essential for this fate determination, but it is selectively required for CD8+ T-cell maturation after commitment directed by T-cell receptors. This indicates that the signals constraining CD4 versus CD8 lineage decisions are distinct from those that support subsequent differentiation events such as silencing of co-receptor loci.
Source PubMed, pmid10761920 doi: 10.1038/35006664
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