1. Assembly and signal transduction of the T cell receptor for antigen.
To examine the role of the CD3 genes in thymocyte development and in T cell function we study mice in which the CD3 genes have been eliminated by homologous recombination techniques. Interestingly, overexpression of CD3epsilon initiates T lymphomagenesis at a very high frequency in transgenic mice made with different constructs.
2. Influence of the co-stimulators SLAM and CD38 on TCR and BCR cell signal transduction.
SLAM and CD38 initiated signal transduction in T and B cells utilizes novel mechanisms not shared by any of the other co-receptors
3. X-linked lymphoproliferative disease (XLP) is a rare disease in which young boys frequently die of fatal infectious mononucleosis and EBV induced lymphomas. We have recently cloned the gene for XLP and found that it binds to a specific site of the cytoplasmic tail of SLAM, a glycoprotein that is expressed on the surface of activated B and T cells. SAP, comprising an SH2-domain and a very short tail acts as an inhibitor molecule by blocking recruitment of other SH2-domain containing signal transduction molecules to a docking site in the SLAMcytoplasmic domain. Mice with a targeted disruption in the SAP or the SLAM gene have been generated. These permit a further dissection of the role of these genes in the immune defense against viruses.
4. Animal models of Inflammatory Bowel Disease.
Three models for experimental enterocolitis are used in the Terhorst lab, one is based on bone marrow transplantation, a second uses adoptive transfers of T cell subsets and a third uses the mutations bred into the IL-2null mouse which develops spontaneous chronic colitis.
5. Interplay between NK cells and T lymphocytes.
Mice that are deficient in NK cells are used to study innate immune responses to viruses and parasites.