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

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 signalling. TCR-complex stimulation resulted in the upregulation of a large number of genes but also in repressing a similar number of genes. PD-1 and BTLA signals attenuated transcriptomic changes mediated by TCR-complex signalling: upregulated genes tended to be suppressed and the expression of a significant number of downregulated genes was higher during PD-1 or BTLA signalling. 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 signalling.