T-Lymphocyte activation; cell-cell interaction and trans-membrane signaling. Work in our laboratory focuses on understanding the requirements for activating T-lymphocytes. T-cell activation involves several different receptors on the T-cell interacting with their ligands on the antigen-bearing cell and with cytokines. We are analyzing the contributions of the various receptors to cell-cell adhesion, signal generation and activation of proliferation and differentiation programs using artificial membrane constructs having purified ligands incorporated onto their surfaces. This is allowing us to define the biochemical signaling events (kinase activation, Ca2+ changes, lipid hydrolysis, etc.) contributed by each receptor and examine the cooperative effects of engaging multiple receptors. In related work, we are using methods of cellular immunology to determine the qualitative and quantitative functional consequences of activating T cells with defined ligands in both in vitro and in vivo model systems. New insights into the requirements for T cell activation gained in these studies are being applied to the development of novel approaches to tumor immunotherapy in both murine models and clinical trials.
Dr. Mescher briefly outlines his current research in the following “Expert Guide” video:
Educational Background
Hope College, Holland, MI (1970), B.A. (Chemistry)
Harvard University, Cambridge, MA (1976), Ph.D. (Biochemistry)
Professional Background
Instructor , Harvard Medical School, Boston, MA, Department of Pathology, 1976 - 1977
Assistant Professor, Harvard Medical School, Boston, MA, Department of Pathology, 1977 - 1983
Associate Professor, Harvard Medical School, Boston, MA, Department of Pathology, 1983 - 1985
Chief and Member, Medical Biology Institute, LaJolla, CA, Division of Membrane Biology, 1985 - 1992
Professor and Virginia and David C. Utz Land Grant Chair in Fundamental Immunobiology, University of Minnesota Medical School, Minneapolis, MN, Department of Laboratory Medicine and Pathology, 1993 - present
Professor, University of Minnesota Medical School, Minneapolis MN, Department of Biochemistry, 1994 - present
Director, University of Minnesota Medical School, Center for Immunology, 1995 - present
Professional Memberships
American Association of Immunologists, 1979 - present
American Society for Cell Biology, 1980 - present
American Chemical Society, 1984 - present
Member, Allergy and Immunology Study Section, 1990 - 1995
Virginia and David C. Utz Land Grant Chair in Fundamental Immunobiology (endowed chair), 1993 - present
Publications
Agarwal P, Raghavan A, Nandiwada SL, Curtsinger JM, Bohjanen PR, Mueller DL, Mescher MF. Gene regulation and chromatin remodeling by IL-12 and type I IFN in programming for CD8 T cell effector function and memory. J Immunol. 2009 Aug 1;183(3):1695-704.
Xiao Z, Casey KA, Jameson SC, Curtsinger JM, Mescher MF. Programming for CD8 T cell memory development requires IL-12 or type I IFN. J Immunol. 2009 Mar 1;182(5):2786-94.
Gerner MY, Mescher MF. Antigen processing and MHC-II presentation by dermal and tumor-infiltrating dendritic cells. J Immunol. 2009 Mar 1;182(5):2726-37.
Gerner MY, Casey KA, Mescher MF. Defective MHC class II presentation by dendritic cells limits CD4 T cell help for antitumor CD8 T cell responses. J Immunol. 2008 Jul 1;181(1):155-64.
Dudek AZ, Mescher MF, Okazaki I, Math VT, Luo X, Curtsinger JM, Miller JS. Autologous large multivalent immunogen vaccine in patients with metastatic melanoma and renal cell carcinoma. Am J Clin Oncol. 2008 Apr;31(2):173-81.
Hammerbeck CD, Mescher MF. Antigen controls IL-7R alpha expression levels on CD8 T cells during full activation or tolerance induction. J Immunol. 2008 Feb 15;180(4):2107-16.
Xiao Z, Mescher MF, Jameson SC. Detuning CD8 T cells: down-regulation of CD8 expression, tetramer binding, and response during CTL activation. J Exp Med. 2007 Oct 29;204(11):2667-77.
Mescher MF, Popescu FE, Gerner M, Hammerbeck CD, Curtsinger JM. Activation-induced non-responsiveness (anergy) limits CD8 T cell responses to tumors. Semin Cancer Biol. 2007 Aug;17(4):299-308.
For a complete listing of Dr. Mescher's publications, please see the National Library of Medicine's PubMed Search.
