Rolf König, Ph.D.
Associate Professor, Dept. of Microbiology and Immunology, Sealy Center for Molecular Medicine, Scientist, Sealy Center for Vaccine Development
RESEARCH INTERESTS AND ACTIVITIES
- Molecular and cellular analysis of T lymphocyte activation, differentiation and apoptosis.
- Functional genomics of inflammation and autoimmune diseases.
- T lymphocyte responses to pathogenic bacteria and their toxins.
- Immunomodulation in vivo and in vitro.
Research activities in this laboratory concentrate on elucidating the molecular events that regulate T lymphocyte activation and tolerance, and the differentiation of T lymphocytes into functional subsets. T lymphocytes initiate immune responses after interaction of the antigen-specific T cell receptor (TCR) with antigenic peptide presented by molecules of the major histocompatibility complex (MHC). Whether the resulting cellular response leads to proliferation of T lymphocytes and production of cytokines, or to T cell tolerance depends on coreceptor and costimulatory molecules that must interact with their respective ligands to enhance and modify TCR-mediated signals. In addition, cytokines and other factors (e.g., bacterial toxins - such as anthrax edema and lethal factor - or tumor cell-secreted factors) present in the microenvironment of the stimulated T cells control their differentiation. Emphasis is on cellular signaling events (e.g., calcium flux, cAMP/PKA, protein tyrosine kinases).
Another major emphasis in the lab is to identify the antigens formed by exposure to environmental chemicals (halogenated alkenes and related substances), and the inflammatory responses and autoimmune diseases induced by these chemicals. Methods used include the isolation of lymphocytes and their stimulation with various antigens, followed by multiplex fluorescent cytokine analysis and functional genomics approaches to identify affected signaling pathways.
Selected Publications
W. Zhou and R. König (2003) T cell receptor-independent CD4 signaling: CD4-MHC class II interactions regulate intracellular calcium and cyclic AMP. Cell. Signal. 15: 751-762.
T. L. Denning, H. Qi, R. König, K. G. Scott, M. Naganuma, and P. B. Ernst (2003) CD4+ Th cells resembling regulatory T cells that inhibit chronic colitis differentiate in the absence of interactions between CD4 and class II MHC. J. Immunol. 171: 2279-2286.
R. König and W. Zhou (2004) Signal transduction in T helper cells: CD4 co-receptors exert complex regulatory effects on T cell activation and function. Curr. Issues Mol. Biol. 6: 1-15.
W. Zhou, L. Vergara, and R. König (2004) T cell receptor-induced intracellular redistribution of type I protein kinase A. Immunology 113: 453-459.
J. E. Comer, A. K. Chopra, J. W. Peterson, and R. König (2005) Direct inhibition of T lymphocyte activation by anthrax toxins in vivo. Infect. Immun. 73: 8275-8281.
P. Cai, R. König, M. F. Khan, S. Qiu, B. S. Kaphalia, and G. A. Ansari (2006). Autoimmune response in MRL +/+ mice following treatment with dichloroacetyl chloride or dichloroacetic anhydride. Toxicol. Appl. Pharmacol. 216: 248-255.