LI scientists have made important contributions to the development of our contemporary understanding of immunobiology and the pathogenesis of immunologic diseases as well as to basic aspects of molecular immunology and immunogenetics. LI researchers have identified the regions of the IL-4 receptor controlling cell growth versus differentiation, demonstrated the critical roles that the cytokine environment plays in the differentiation of naive CD4 T cells into TH1 or TH2 cells, characterized the phenotype of T cells involved in spontaneous multiorgan autoimmune disorders, and discovered a novel role for NK1.1 T cells recognizing CD1 in the production of IL-4 and other cytokines.
LI investigators have discovered TCR antagonists and obtained evidence for altered early tyrosine phosphorylation upon TCR engagement by such variant ligands, measured the kinetics of peptide-MHC class I binding to and dissociation from soluble TCR, localized the sites of CD4:MHC class II interaction, described novel targeting signals involved in control of intracellular MHC molecule trafficking, generated bioactive soluble TCR, and designed highly efficient oligomeric carriers for vaccine antigens.
Studies of T-cell apoptosis have resulted in identification of mutations in fas in humans with autoimmune/lymphoproliferative syndrome (ALPS) and the description of the apoptotic mechanisms involved in T-cell death induced by antigen recognition.
Work on lymphocyte development has led to characterization of a novel positive selection process during B-cell development, evidence for a role for purinergic receptors in thymocyte selection and T-cell activation, and identification of the cytokines regulating the choice between the T-cell and NK-cell lineages.
Future efforts by LI scientists in these rapidly moving areas will include tracking of antigen-presenting cells in vivo, characterization of the role of individual TCR components in specific signaling events and biological functions, identification of intracellular proteins involved in transducing death signals in T cells, manipulation of key intracellular signaling molecules in vivo using novel methods of gene targeting and transgenesis, investigation of the ligands involved in driving B-cell- and T-cell-positive selection, cloning of genes involved in lymphocyte lineage fate determination, dissection of the role of purinergic receptors in T-cell development and mature function, measurement of the interactions between TCR and altered receptor ligands and correlation of these data with the signaling and biological properties of such ligands, crystallographic description of TCR and TCR-ligand complexes, examination of the biochemical and molecular basis for Th1 versus Th2 phenotypes, dissection of the mechanism of cytokine receptor signal transduction, and investigation of the cellular events involved in development of organ-specific autoimmunity.
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Last Updated May 19, 2006