Prof. Dr.med. Peter H. Krammer was born in Rheydt, Rhineland, Germany. He received his medical training in Freiburg, Germany, St. Louis, USA, and Lausanne, Switzerland. He did his thesis on extracellular streptococcus antigens at the Institute for Microbiology and Hygiene at the University of Freiburg, and investigated the role of small nuclear RNAs at the Institute of Pathology, also in Freiburg. In 1973, at the age of 27, he became a member of the Basel Institute for Immunology and spent almost three fruitful years at the Institute studying T cells and their specificity. From Basel, he moved via the Max-Planck-Institute for Immunobiology in Freiburg, where he stayed one year to continue T cells studies, to Heidelberg to the German Cancer Research Center, where in 1976 he started his work in the Division of Immunogenetics. There, again, his main work was on T cells and T cell clones, their receptor specificities and their activities. Later, in the early 1980s, he focused on T cell-derived cytokines. He investigated the activation of macrophages by macrophage activating factors and in a fruitful, longstanding collaboration with E. Vitetta and her associates from Dallas, discovered IL-4 as a B cell immunoglobulin switch factor. With fondness he remembers his days as a visiting professor in Dallas and the friendliness of the Texans who hosted his stay. In 1984/85, he felt that molecular biology would leave a significant mark on immunology and he spent one and a half years in A. Sippelës laboratory at the Center for Molecular Biology in Heidelberg to learn the thinking and the techniques in this field. In the mid-to-late 1980s, his interest shifted very much towards negative regulation of tumor cell growth and apoptosis. In this context he and his associates discovered the CD95(APO-1/Fas) system, highlighted by the first publication in Science in 1989. CD95, its signalling machinery and its role in physiology and diseases remained at the center of his interest. Peter Krammer has received numerous prizes for his work and is a reviewer for and serves on the editorial board of many journals. Presently, he is the Director of the Tumor Immunology Program of the German Cancer Research Center. He runs a large group of scientists and his main interest is sensitivity and resistance in apoptosis and the role of apoptosis in the immune system and in diseases.
No life without death
CD95, a member of the tumor necrosis factor (TNF) receptor superfamily, induces apoptosis upon receptor oligomerization. The receptor and its ligand are important for apoptosis of peripheral T cells, for downregulation of an immune response and most likely, at least in part, also for peripheral T cell tolerance. In AIDS, apoptosis mediated by this system might contribute to the depletion of T helper lymphocytes. Likewise, in diseases in which liver cells are destroyed, the CD95 system might play a major role. In a search to identify the intracellular signalling pathway of CD95 several molecules coupling to oligomerized CD95 were immunoprecipitated from apoptosis-sensitive human leukemic T cell and lymphoblastoid B cell lines. The following binding molecules were only associated with aggregated and not with monomeric CD95: phosphorylated FADD (MORT1) and caspase 8. Thus, caspase 8 was identified as the most CD95 receptor proximal protease which starts the cascade of protease reactions important for CD95-mediated apoptosis. Association of FADD and caspase 8 with CD95 was not observed with C-terminally truncated non-signalling CD95. FADD and FLICE did also not associate with a CD95 cytoplasmic tail carrying the lprcg amino acid replacement. FADD and caspase 8 form a death-inducing signalling complex (DISC) with the CD95 receptor and are, thus, the first CD95 associating proteins of a signalling cascade mediating apoptosis.The function of the DISC is discussed in detail, particularly with respect to its role in sensitivity and resistance to apoptosis. The CD95 death system plays a role in destruction of liver tissue. In hepatitis cytotoxic T lymphocytes might use the CD95 system to kill infected hepatocytes. In M. Wilson copper overload leads to upregulation of the CD95 ligand that may finally contribute to acute liver failure. In HCC from patients treated with chemotherapeutic drugs the CD95 receptor and ligand are upregulated and may contribute to apoptosis of the tumor or, depending on the drug sensitivity of the tumor, to the status of the tumor as an immunoprivileged site.