The major focus of the Busch laboratory is to visualize and track antigen-specific T cell populations during in vivo antigen challenge to increase our understanding of how T cell responses are regulated in vivo and how protective and long lasting immunity is established. This knowledge is of special interest for adoptive immunotherapy, diagnostic monitoring of T cell mediated immunity, and the development of new vaccination strategies.
Antigen-specific T cell responses are of major importance in the control of infection and the development of protective immunity. T cells can also mediate anti-tumor effects and, in the case of autoimmune syndromes, can contribute to the development and pathology of disease.
Over the last few decades, numerous epitopes recognized by antigen-specific T cells have been identified, and general features of T cell responses revealed. Due to the difficulty of identifying antigen-specific T cells directly ex vivo, however, many basic questions regarding the in vivo regulation of antigen-specific T cell responses and the generation of protective immunity are still unsolved. Using new immunological methods, especially MHC multimer technologies, we are now able to directly identify and isolate T cells depending on their antigen specificity.
The goal of this lab is to further develop these new advances in immunological techniques, to investigate antigen-specific T cell responses in an animal model and to test direct clinical applications of the technology.
Buchholz, V. R., Flossdorf, M., Hensel, I., Kretschmer, L., Weissbrich, B., Graf, P., Verschoor, A., Schiemann, M., Hofer, T., and Busch, D. H. (2013) Disparate Individual Fates Compose Robust CD8+ T Cell Immunity, Science 340(6132):630-5.
Nauerth, M., Weißbrich, B., Knall, R., Franz, T., Dössinger, G., Bet, J., Paszkiewicz, P.J., Pfeifer, L., Bunse, M., Uckert, W., Holtappels, R., Gillert-Marien, D., Neuenhahn, M., Krackhardt, A., Reddehase, M. J., Riddell, S. R., and Busch, D. H. (2013) TCR-ligand koff-rate predicts protective capacity of antigen-specific CD8+ T cells for adoptive transfer. Science Translational Medicine 5(192):192ra87.
Busch D.H., I.M. Pilip, S. Vijh, and Pamer E.G. (1998) Coordinate regulation of complex T cell populations responding to bacterial infection. Immunity 8: 353-362.
Knabel M, Franz TJ, Schiemann M, Wulf A, Villmow B, Schmidt B., Bernhard H., Wagner H, and Busch DH (2002). Reversible MHC multimer staining for functional isolation of T cell populations and effective adoptive transfer. Nature Medicine, 8; 631-637.
Huster K.M., Busch V., Schiemann M., Linkemann K., Kerksiek K.M., Wagner H. and Busch D.H. (2004). Selective expression of IL-7 receptor on memory T cells identifies early CD40L-dependent generation of distinct CD8+ memory T cell subsets. PNAS 101(15):5610-5.
Neuenhahn M., Kerksiek K.M., Nauerth M., Suhre M.H., Schiemann M., Gebhardt F.E., Stemberger C., Panthel K., Schröder S., Chakraborty T., Jung S., Hochrein H., Rüssmann H., Brocker T. , and Busch D.H. (2006) CD8alpha-positive dendritic cells are required for efficient entry of Listeria monocytogenes into the spleen. Immunity Oct;25(4):619-30.
Stemberger C., Huster H., Koffler M., Anderl F., Schiemann M., Wagner H., and Busch D.H. (2007) A single naive CD8+ T cell precursor can develop into diverse effector and memory subsets. Immunity. 2007 Dec;27(6):985-97.