BTLA and PD-1 signals attenuate TCR-mediated transcriptomic changes

Muhammad Zainul Arifin; Judith Leitner; Donagh Egan; Petra Waidhofer-Söllner; Walter Kolch; Vadim Zhernovkov; Peter Steinberger

doi:10.1016/j.isci.2024.110253

BTLA and PD-1 signals attenuate TCR-mediated transcriptomic changes

iScience. 2024 Jun 12;27(7):110253. doi: 10.1016/j.isci.2024.110253. eCollection 2024 Jul 19.

Authors

Muhammad Zainul Arifin¹, Judith Leitner², Donagh Egan¹, Petra Waidhofer-Söllner², Walter Kolch^{1

3}, Vadim Zhernovkov¹, Peter Steinberger²

Affiliations

¹ Systems Biology Ireland, School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
² Center for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Medical University of Vienna, Vienna, Austria.
³ Conway Institute of Biomolecular & Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.

Abstract

T cell co-inhibitory immune checkpoints, such as PD-1 or BTLA, are bona fide targets in cancer therapy. We used a human T cell reporter line to measure transcriptomic changes mediated by PD-1- and BTLA-induced signaling. T cell receptor (TCR)-complex stimulation resulted in the upregulation of a large number of genes but also in repression of a similar number of genes. PD-1 and BTLA signals attenuated transcriptomic changes mediated by TCR-complex signaling: upregulated genes tended to be suppressed and the expression of a significant number of downregulated genes was higher during PD-1 or BTLA signaling. BTLA was a significantly stronger attenuator of TCR-complex-induced transcriptome changes than PD-1. A strong overlap between genes that were regulated indicated quantitative rather than qualitative differences between these receptors. In line with their function as attenuators of TCR-complex-mediated changes, we found strongly regulated genes to be prime targets of PD-1 and BTLA signaling.

Keywords: Molecular biology; Transcriptomics.