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| Frontiers in immunology. 2022 Aug 23. doi: 10.3389/fimmu.2022.956694. pmc: PMC9446882 |
| BTLA inhibition has a dominant role in the -complex of BTLA and HVEM. |
| Battin C1, Leitner J2, Waidhofer-Söllner P3, Grabmeier-Pfistershammer K4, Olive D5, Steinberger P6 |
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Abstract The engagement of the herpesvirus entry mediator (HVEM, TNFRSF14) by the B and T lymphocyte attenuator (BTLA) represents a unique interaction between an activating receptor of the TNFR-superfamily and an inhibitory receptor of the Ig-superfamily. BTLA and HVEM have both been implicated in the regulation of human T cell responses, but their role is complex and incompletely understood. Here, we have used T cell reporter systems to dissect the complex interplay of HVEM with BTLA and its additional ligands LIGHT and CD160. Co-expression with LIGHT or CD160, but not with BTLA, induced strong constitutive signaling HVEM. In line with earlier reports, we observed that interaction of BTLA and HVEM prevented HVEM co-stimulation by ligands on surrounding cells. Intriguingly, our data indicate that BTLA mediated inhibition is not impaired in this heterodimeric complex, suggesting a dominant role of BTLA co-inhibition. Stimulation of primary human T cells in presence of HVEM ligands indicated a weak costimulatory capacity of HVEM potentially owed to its engagement by BTLA. Furthermore, experiments with T cell reporter cells and primary T cells demonstrate that HVEM antibodies can augment T cell responses by concomitantly acting as checkpoint inhibitors and co-stimulation agonists. |
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Copyright © 2022 Battin, Leitner, Waidhofer-Söllner, Grabmeier-Pfistershammer, Olive and Steinberger. |
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KEYWORDS: BTLA, CD160, HVEM/TNFRSF14, LIGHT, T cell inhibition, human T cell costimulation |
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Publikations ID: 36081508 Quelle: öffnen |
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