CD28 and TCR differentially impact naïve and memory T cell responses.

Manipulating CD28 co-stimulation is a key element of anti-tumour immune responses and treating autoimmune diseases. CD28 can reduce the T cell activation threshold but has a complex relationship with T cell receptor (TCR) signalling and an unclear role in specific T cell subsets. Using a series of stimulation assays, we have studied the relative contribution of CD28 and TCR signals in human CD4 + T cell responses.

The CTLA-4 immune checkpoint protein regulates PD-L1:PD-1 interaction via transendocytosis of its ligand CD80.

CTLA-4 and PD-1 are key immune checkpoint receptors that are targeted in the treatment of cancer. A recently identified physical interaction between the respective ligands, CD80 and PD-L1, has been shown to block PD-L1/PD-1 binding and to prevent PD-L1 inhibitory functions. Since CTLA-4 is known to capture and degrade its ligands via transendocytosis, we investigated the interplay between CD80 transendocytosis and CD80/PD-L1 interaction.

Impact of CTLA-4 checkpoint antibodies on ligand binding and Transendocytosis.

Anti-CTLA-4 antibodies have pioneered the field of tumour immunotherapy. However, despite impressive clinical response data, the mechanism by which anti-CTLA-4 antibodies work is still controversial. Two major checkpoint antibodies (ipilimumab and tremelimumab) have been trialled clinically.