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The duration of antigen receptor signalling determines CD4+ versus CD8+ T-cell lineage fate.
Nature. 2000 Mar 30; 404(6777):506-10.Nat

Abstract

Signals 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.

Authors+Show Affiliations

Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10761920

Citation

Yasutomo, K, et al. "The Duration of Antigen Receptor Signalling Determines CD4+ Versus CD8+ T-cell Lineage Fate." Nature, vol. 404, no. 6777, 2000, pp. 506-10.
Yasutomo K, Doyle C, Miele L, et al. The duration of antigen receptor signalling determines CD4+ versus CD8+ T-cell lineage fate. Nature. 2000;404(6777):506-10.
Yasutomo, K., Doyle, C., Miele, L., Fuchs, C., & Germain, R. N. (2000). The duration of antigen receptor signalling determines CD4+ versus CD8+ T-cell lineage fate. Nature, 404(6777), 506-10.
Yasutomo K, et al. The Duration of Antigen Receptor Signalling Determines CD4+ Versus CD8+ T-cell Lineage Fate. Nature. 2000 Mar 30;404(6777):506-10. PubMed PMID: 10761920.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The duration of antigen receptor signalling determines CD4+ versus CD8+ T-cell lineage fate. AU - Yasutomo,K, AU - Doyle,C, AU - Miele,L, AU - Fuchs,C, AU - Germain,R N, PY - 2000/4/13/pubmed PY - 2000/4/29/medline PY - 2000/4/13/entrez SP - 506 EP - 10 JF - Nature JO - Nature VL - 404 IS - 6777 N2 - Signals 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. SN - 0028-0836 UR - https://www.unboundmedicine.com/medline/citation/10761920/The_duration_of_antigen_receptor_signalling_determines_CD4+_versus_CD8+_T_cell_lineage_fate_ L2 - https://doi.org/10.1038/35006664 DB - PRIME DP - Unbound Medicine ER -