The Parker laboratory is interested in the cell-surface molecules and intracellular signaling pathways which determine whether an encounter between helper T cells and B cells or other antigen presenting cells results in immunity or tolerance. In a simplified model of peripheral tolerance to self, the Parker lab found that a signal through OX40 (CD134) blocks functional anergy in transferred T cells responding to transgenic or allogeneic antigens, drives the T cells to differentiate into cytokine-secreting effector cells, and results in fatal acute graft versus host disease in unirradiated recipient animals. Current work is focused on the role of NIK and the non-canonical pathway of NFκB activation in this signal through OX40 and other TNF receptor family members. For more detail on this project, see theResearch Interests page for Dr. Susan Murray under Research Faculty. In a second project, the lab is exploring the "immunological synapse", the structure that forms in the contact zone between a T cell and an antigen presenting cell. We are examining the role of the synapse in the specific delivery of the membrane-bound TNF family member, CD40L (CD154), that is necessary for T cell activation of B cells in the antibody response. We are also exploring differences among T cell subsets in the structure of the synapse and the functional consequences of those differences.
Th1 (A) and Th2 cells (B) were incubated on supported planar lipid bilayers containing ICAM-1-Cy5 (red) and peptide- loaded I-Ek-488 (green) for 20 min before imaging. From Thauland TJ et al. (2008) J Immunol 181: 393.