Anton van der Merwe
Molecular analysis of leucocyte recognition
My group studies the mechanisms by which leukocytes, such as T cells, use cell surface receptors to recognise infected or cancerous cells. The T cell receptor (TCR) plays a major role in this process by probing the surfaces of cells for the presence of 'foreign' peptides presented on MHC molecules in a peptide-MHC (pMHC) complex. A major focus of our work is to understand how the binding of TCRs to foreign pMHC leads to T cell activation. We have proposed a novel mechanism of TCR signal transduction, termed the kinetic-segregation (KS) model. One focus of our work is testing this model.
A large number (>120) of leukocyte cell-surface receptors share key similarities with the TCR, suggesting that they signal by the same mechanism. A second focus of our work is to explore this possibility.
Many leukocyte receptors are inhibitory and block activation through activatory receptors. Blocking these receptors has been shown to enhance immune response to cancer. We are investigating the mechanisms by which activatory and inhibitory receptors integrate their signals when they engage ligands.