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Matthew F. Mescher, Ph.D.
Professor and Kimmelman Chair in Immunology
Department of Laboratory Medicine and Pathology
Harvard University, 1976, Ph.D.
mesch001@umn.edu
612-626-2368, 612- 626-2403 - office
612-626-2476 - lab
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Research Interests:
Cytotoxic T lymphocyte activation, signal transduction, immunotherapy
The cytotoxic T lymphocyte (CTL), also known as the killer
cell, plays an important role in immune defense by directly
binding to and killing tumor or virus-infected cells. Dr.
Mescher's laboratory focuses on cell surface receptor interactions
and signaling pathways involved in activation of CTLs. Immunologists
have found that the antigen recognized by the T cell receptor
consists of a peptide bound to major histocompatibility complex
protein on the surface of the target cell. This recognition
initiates a cascade of adhesion and transmembrane signaling
events involving several different receptors on the CTL binding
to cell surface ligands on the target cells. Mescher and his
colleagues are using novel methods for producing artificial
lipid membrane constructs from purified membrane proteins
to sort out these complex signaling events. Molecules known
to be involved in CTL binding and signal transduction, such
as ligands for CD8 proteins and integrins, can be selectively
introduced into these membranes and their specific role in
CTL binding, response, and membrane-cytoskeletal interactions
can be studied. Mescher's work on the molecular basis of T
cell activation has important implications for the development
of novel therapeutic approaches for activating tumor and virus-specific
CTL responses. Artificial membranes made in his laboratory
for in vitro studies of T cell activation augment CTL response
in mice in an antigen-specific manner. The researchers are
now trying to determine how antigen-bound artificial membranes,
particularly membrane-coated latex microspheres, mediate CTL
enhancement and produce therapeutic effects. These findings
would allow for further exploration of the potential for this
approach to immunization and disease therapy.
Selected Recent Publications:
- Mescher, M., and Rogers, J. (1996). Immunotherapy of
established murine tumors with large multivalent immunogen
and cyclophosphamide. J.
Immunother. 19, 102-112.
- Curtsinger, J.M., C.S. Schmidt, A. Mondino, D.C. Lins,
R.M. Kedl, M.K. Jenkins and M.F. Mescher (1999) Inflammatory
cytokines provide a third signal for act of naive CD4+ and
CD8+ T cells. J.
Immunol. 162:3256-3262.
- Shrikant, P., A. Khoruts and M.F. Mescher (1999) CTLA-4
blockade reverses CD8+ T cell tolerance to tumor by a CD4+
T cell and IL-2-dependent mechanism.
Immunity 11:483-493.
- Tham,E.L. and M.F.Mescher. (2001) Signaling alterations
in activation-induced non-responsive (AINR) CD8 T cells.
J.
Immunol. 167:2040-2048.
- Tham,E.L., P.Shrikant and M.F.Mescher. Activation-induced
nonresponsiveness: a Th-dependent regulatory checkpoint
in the CTL response. J.
Immunol. 168: 1190-1197, 2002.
- Schmidt,C.S. and M.F.Mescher. Peptide Ag priming of naÔve,
but not memory, CD8 T cells requires a third signal that
can be provided by IL-12. J.
Immunol., 168:5521-5529, 2002.
- Curtsinger,J.M., D.C.Lins and M.F.Mescher. Signal three
determines tolerance versus full activation of naïve
CD8 T cells: dissociating proliferation and development
of effector function. J.
Exp. Med. 197: 1141-1151, 2003.
- Valenzuela, J., C.Hammerbeck and M.F.Mescher. Cutting Edge: Bcl-3 upregulation by signal 3 cytokine (IL-12) prolongs survival of Ag-activated CD8 T cells. J. Immunol. 174: 600-604, 2005.
- Curtsinger, J.M., J.O. Valenzuela, P. Agarwal, D. Lins and M.F. Mescher. Cutting Edge: Type I interferons provide a third signal to CD8 T cells to stimulate clonal expansion and differentiation. J. Immunol. 174:4465-4469. 2005.
Last updated: October 17, 2005
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