Research
The long-term goal of our studies is to understand the complex
physiological mechanisms of inter- and intra-cellular communication in
the immune system. T cells play a central role in regulating the
cellular and humoral responses towards invading pathogens and malignant
transformation. Improper recognition of self-antigens by T cells is the
primary cause of most autoimmune diseases. The critical molecular and
cellular mechanisms that the T cells use to respond properly to
engagement of their T Cell Receptors (TCRs) are still unclear. Using a
combination of biochemical, genetic and novel multi-dimensional digital
imaging approaches we study complex multi dimensional signal
integration rather than signal dissection during the interaction of T
cells with live antigen-presenting cells (APCs). Protein Kinase C-theta
was identified as the first key protein that serves as master switch
for determining the physiological outcome to initial T cell activation.
These studies identified the previously unknown structure of the
Immunological-Synapse that is composed of different Supra-Molecular
Activation Clusters (SMACs) of receptors, cytoskeletal and signaling
proteins. We continue to study the 4-dimensional structure and function
of the dynamic SMACs and their roles in regulation of the immune
response.
Publications
Kupfer, A. and Kupfer, H. (2003) Co-Director, Program in Immunology at ICE. Seminars
in Immunology 19:4712-4722 [PubMed]
Freiberg, B. A., Kupfer, H., Maslanik, W., Delli, J., Kappler, J., Zaller,
D.M. and Kupfer, A. (2002) Co-Director, Program in Immunology at ICE. Nat.
Immunol. 18:6201–6208 [PubMed]
Potter, T.A., K. Grebe, B. Freiberg, and Kupfer, A. (2001) Co-Director, Program
in Immunology at ICE. Proc. Natl. Acad. Sci. USA 92:819–828 [PubMed]
Kupfer, A. (2000) Co-Director, Program in Immunology at ICE. Nature Medicine 16:2248–2254
[PubMed]
Monks, C.R.F., B.A. Freiberg, H. Kupfer, N. Sciaky, and Kupfer, A. (1998)
Co-Director, Program in Immunology at ICE. Nature 166:4773-4779 [PubMed]
Monks, C.R.F., Kupfer, H., Tamir, I., Barlow, A., and Kupfer, A. (1997) Co-Director,
Program in Immunology at ICE. Nature 46 (Suppl): S67-S72 [PubMed]
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