Led by Prof. Tao Dong (CAMS Oxford Institute (COI) & MRC Translational Immune Discovery Unit (TIDU)), Prof. Michael Dustin (Kennedy Institute and COI), Dr Megat Abd Hamid (COI) & Dr Pablo Cespedes (COI), researchers have discovered that tumour-specific T cells expressing the integrin CD103 can also express CD61, an integrin previously only well-documented in non-lymphocytic cells. They found that the presence of CD61 at the synapse between T cells and antigen-presenting cells can modulate T cell receptor (TCR) signalling to improve anti-tumour cytotoxicity and promote control of tumour growth.
Integrins are large, heterodimeric transmembrane glycoproteins that facilitate adhesion between cells, and with the extracellular matrix. They require the pairing between an a-and b-subunit to exit the endoplasmic reticulum and reach the cell surface to become functionally active. CD103, or integrin aE, usually pairs with integrin b7 on human immune cells, but here they show that it pairs with CD61, or integrin b3, instead. This is the first evidence of CD61 expression on human cytotoxic T cells.
The interaction between CD103 and CD61 occurs in the central synapse point of interaction between the T cell and antigen-presenting cell. TCRs are also present in this area where they interact with peptide-MHC complexes for activation of the T cells. The researchers found that CD61 presence at the synapse increased TCR signalling and T cell activation which in turn led to better control of tumour growth in a mouse model.
Read more on the CAMS COI website: https://www.camsoxford.ox.ac.uk/news/novel-pairing-of-integrins-improves-action-of-t-cells-on-cancer-cells-to-control-tumour-growth
The full article can be found here.