Molecular Immunology

The laboratory has an interest in uncovering the receptors and signaling mechanisms that regulate T-cell function. We first showed that the CD4 and CD8 co-receptors are coupled to the lymphoid specific protein-tyrosine kinase p56lck, and that these complexes phosphorylate TcRzeta and CD3 chains. CD4-p56lck and CD8-p56lck complexes are now widely accepted as the initiators of T-cell activation. Targets of kinases include a growing family of immune cell specific adaptor proteins (VAV, LAT, SLP-76, GADS, ADAP and SKAP-55) that have the potential to integrate cell surface events with downstream effector functions. Recently, we have demonstrated that adaptors ADAP and SKAP-55 regulate integrin adhesion and clustering and the ability of T-cells to form conjugates with antigen-presenting cells, a central event in the regulation of the immune response.

T cells

In an equally important area, we are also interested in co-receptors CD28, ICOS and CTLA-4, receptors that provide key second signals in determining the ultimate outcome of the activation process. We first showed that co-receptors act as major reservoir for the lipid kinase phosphatidylinositol 3-kinase (PI-3 kinase). Present studies involve investigating the downstream targets of the co-receptor-PI 3K pathway, independent pathways and the basis for negative signalling by CTLA-4.