Soluble PD-L1 generated by endogenous retroelement exaptation is a receptor antagonist.
| Autor: | Ng KW; Retroviral Immunology, The Francis Crick Institute, London, United Kingdom., Attig J; Retroviral Immunology, The Francis Crick Institute, London, United Kingdom., Young GR; Retrovirus-Host Interactions, The Francis Crick Institute, London, United Kingdom., Ottina E; Retroviral Immunology, The Francis Crick Institute, London, United Kingdom., Papamichos SI; Department of Haematology, Democritus University of Thrace Medical School, Alexandroupolis, Greece., Kotsianidis I; Department of Haematology, Democritus University of Thrace Medical School, Alexandroupolis, Greece., Kassiotis G; Retroviral Immunology, The Francis Crick Institute, London, United Kingdom.; Department of Medicine, Faculty of Medicine, Imperial College London, London, United Kingdom. |
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| Jazyk: | angličtina |
| Zdroj: | ELife [Elife] 2019 Nov 15; Vol. 8. Date of Electronic Publication: 2019 Nov 15. |
| DOI: | 10.7554/eLife.50256 |
| Abstrakt: | Immune regulation is a finely balanced process of positive and negative signals. PD-L1 and its receptor PD-1 are critical regulators of autoimmune, antiviral and antitumoural T cell responses. Although the function of its predominant membrane-bound form is well established, the source and biological activity of soluble PD-L1 (sPD-L1) remain incompletely understood. Here, we show that sPD-L1 in human healthy tissues and tumours is produced by exaptation of an intronic LINE-2A ( L2A ) endogenous retroelement in the CD274 gene, encoding PD-L1, which causes omission of the transmembrane domain and the regulatory sequence in the canonical 3' untranslated region. The alternatively spliced CD274-L2A transcript forms the major source of sPD-L1 and is highly conserved in hominids, but lost in mice and a few related species. Importantly, CD274-L2A -encoded sPD-L1 lacks measurable T cell inhibitory activity. Instead, it functions as a receptor antagonist, blocking the inhibitory activity of PD-L1 bound on cellular or exosomal membranes. Competing Interests: KN, JA, GY, EO, SP, IK, GK No competing interests declared (© 2019, Ng et al.) |
| Databáze: | MEDLINE |
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