Thomas Proft - InvitrogenTM Award 2004

Thomas Proft
Position: Senior Research Fellow
Extn: 86213
Email: t.proft@auckland.ac.nz
Research Group: Molecular Immunology

Research Interests

I am a Molecular Microbiologist with an MSc (1991) and PhD (1995) from the University of Heidelberg, Germany. During my postgraduate studies, I investigated a set of novel proteins that are involved in a cytoskeleton-like structure of the wall-less bacterium Mycoplasma pneumoniae. My current interests are focussed on virulence mechanisms of the human pathogens Streptococcus pyogenes and Staphylococcus aureus with particular interest in secreted protein toxins, such as superantigens. In contrast to conventional antigens, superantigens are not processed inside antigen presenting cells (APCs), but instead directly bind to the major histocompatibility complex class II protein (MHC II) outside the antigen-binding groove. Simultaneously, they bind to all T cell receptors (TCRs) bearing particular Vb regions. This trimolecular complex subsequently cross-links a large number of APCs and T cells resulting in massive over-stimulation of the cellular immune response, with the production of high systemic levels of the cytokines TNF-a and IL-1b and of T cell mediators, such as IL-2 and IFN-g. This activity is central to their involvement in many human diseases, such as toxic shock, scarlet fever, and possibly others such as autoimmune diseases.

Collaborators

Prof. Edward N. Baker, Dr. Heather Baker, Dr. Vic Arcus School of Biological Sciences, University of Auckland

A/Prof. Mark Thomas, Dr. David Holland Department of Molecular Medicine & Pathology, University of Auckland

Dr. Shiranee Sriskandan Imperial College, London, U.K.

Dr. Bjoern K.G. Eriksson Dept. of Infectious Diseases, Karolinska Institute, Huddinge University, Sweden

Prof. Lothar Rink Institute of Immunology, University of Aachen, Germany

Selected Publications

• Proft, T., Fraser, J.D. 'Superantigens: Just like peptides only different', Journal of Experimental Medicine, 187, p819-821, 1998
• Proft, T., Moffatt, S.L., Berkahn, C.J., Fraser, J.D. 'Identification and characterization of novel superantigens from Streptococcus pyogenes', Journal of Experimental Medicine, 189, p89-101, 1999
• Bernal, A., Proft, T., Fraser, J.D., Posnett, D.N. 'Superantigens in human disease', Journal of Clinical Immunology, 19, (3), p149-157, 1999
• Arcus, V.L., Proft, T., Sigrell, J.A., Baker, H.M., Fraser, J.D., Baker, E.N. 'Conservation and variation in superantigen structure and activity highlighted by the three-dimensional structures of two new superantigens from Streptococcus pyogenes', Journal of Molecular Biology, 299, p157-168, 2000
• Fraser, J.D., Arcus, V.L., Kong, P., Baker, E.N., Proft, T. 'Superantigens - powerful modifiers of the immune system', Molecular Medicine Today, 6, (3), p125-132, 2000
• Lei, L., Altstaedt, J., Gerke, M., Proft, T., Rink, L. 'Induction of IL-8 on Human Neutrophils following MHC class II cross-linking with Superantigens.', Journal of Leukocyte Biology, 70, (1), p80-86, 2001
• Mueller-Alouf, H., Proft, T., Zollner, T.M., Gerlach, D., Champagne, E., Desreumaux, P., Fitting, C., Geoffroy-Fauvet, C., Alouf, J.E., Cavaillon, J.M. 'Pyrogenicity and Cytokine-Inducing Properties of Streptococcus pyogenes superantigens: Comparative study of Streptococcal Mitogenic Exotoxin Z and Pyrogenic exotoxin A.', Infection and Immunity, 69, (6), p4141-4145, 2001
• Proft, T., Arcus, V.L., Handley, V., Baker, E.N., Fraser, J.D., Immunological and Biochemical Characterisation of Streptococcal Pyrogenic Exotoxins I and J (SPE-I and SPE-J) from Streptococcus pyogenes, Journal of Immunology, 166, p6711-6719, 2001
• Langley, R.J., Arcus, V.L., Proft, T., Fraser, J.D., Baker, E.N. 'The Three-dimensional structure of a superantigen-like protein, SET3, from a pathogenicity island of the Staphylococcus aureus genome', Journal of Biological Chemistry, 277, (35), p32274-32281, 2002
• Arcus, V.L., Langley, R.J., Proft, T., Fraser, J.D., Baker, E.N. 'The three-dimensional structure of a superantigen-like protein, SET3, from a pathogenicity island of the Staphylococcus aureus genome', Journal of Biological Chemistry, 277, p32274-32281, 2002
• Unnikrishnan, M., Altmann, D.M., Proft, T., Wahid, F., Cohen, J., Fraser, J.D., Sriskandan, S. 'The bacterial superantigen streptococcal mitogenic exotoxin Z is the major immunoactive agent of Streptococcus pyogenes', Journal of Immunology, 169, p2561-2569, 2002
• Proft, T., Webb, P.D., Handley, V., Fraser, J.D. 'Two Novel Superantigens Found in Both Group A and Group C Streptococcus', Infection and Immunity, 71, (3), p1361-1369, 2003
• Proft, T., Fraser, J.D. 'Bacterial Superantigens', Clinical and Experimental Immunology, 133, (3), p299-306, 2003
• Proft, T., Sriskandan S., Yang L., Fraser J.D., Superantigens and Streptococcal Toxic Shock Syndrome, Emerging Infectious Diseases, 9, (10), p1211-1218, 2003
• Baker, H.M, Proft, T., Webb, P.D., Arcus, V.L., Fraser, J.D., Baker, E.N., Crystallographic and mutational data show that the Streptococcal Pyrogenic Exotoxin J Can Use a Common Binding Surface for T-Cell Receptor Binding and Dimerization, Journal of Biological Chemistry, 279, (37), p38571-38576, 2004
• Yang, L.P., Thomas, M.G., Woodhouse, A., Martin, D., Fraser, J.D., Proft, T. 'Involvement of streptococcal mitogenic exotoxin Z in streptococcal toxic shock syndrome', Journal of Clinical Microbiology, 43, p3570-3573, 2005
• Yang, L.P., Eriksson, B.K., Harrington, Z., Curtis, N., Lang, S., Currie, B.J., Fraser, J.D., Proft, T. 'Variations in the protective immune response against streptococcal superantigens in populations of different ethnicity', Medical Microbiology and Immunology, 194, (5), p1-7, 2005
• Schrage, B., Duan, G., Yang, L.P., Fraser, J.D. And Proft, T. 'Different preparations of intravenous immunoglobulin vary in their efficacy to neutralize streptococcal superantigens - implications for treatment of streptococcal toxic shock syndrome.', Clinical Infectious Diseases, in press

Book chapters

• Fraser, J.D., Proft, T., Arcus, V.L., Baker, E.N. 'Bacterial superantigens and immune evasion', In:B. Henderson and P.C.F. Oysten(ed.), Bacterial Evasion of Host Immune Responses.., Cambridge, Cambridge University Press, p.171-200, 2003
• Proft, T., Schrage, B., Fraser, J.D. 'Superantigens - Microbial toxins that target the immune system', In:Proft T.(ed.), Microbial Toxins - Molecular and Cellular Biology., (1.edn), Wymondham, U.K., Horizon Bioscience, p.179-214, 2005
• Proft, T.., Fraser, J.D. 'Streptococcal Superantigenic Toxins.', In:Alouf JJ, Popoff M.(eds.), The Comprehensive Sourcebook of Bacterial Protein Toxins., (3rdedn), London, Academic Press, p.844-861, 2005
• Proft, T., Fraser, J.D. 'Streptococcal Superantigens: An Update.', In:Kotb M and Fraser JD(eds.), Superantigens: Molecular basis for their role in human diseases., ASM Press, in press
• Proft, T., Fraser, J.D. 'Streptococcal Superantigens', In:Marone G(ed.), Superantigens and Superallergens., (1.edn), Basel, Karger, in press