Infection and Immunology

Busch, Dirk

Investigation of antigen-specific T cell responses for the development of novel immunotherapies

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.

Selected publications:

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.