Gilles Benichou

Associate Professor, HMS
Associate Scientist and Director of Molecular and Cellular Immunology Laboratory

Massachusetts General Hospital
Department of Surgery
Boston, MA 02114
Tel: 617-724-4206
email:GBenichou@partners.org

Fellows currently in my laboratory:

Our research is focused on the mechanisms involved in the induction and the regulation of T cell responses in vivo to protein and peptides antigens. We have designed a series of models to understand the mechanisms underlying the recognition of peptide antigens by T cells in vivo and its influence on immune rejection and tolerance. To address this question, we are testing T cell responses to self- and non-self determinants present on transplantation and tumor antigens.

Area 1: Allotransplantation T lymphocytes recognize transplantation antigens via two distinct pathways: direct allorecognition, in which T cells interact with intact allogeneic MHC molecules on donor cells and, indirect allorecognition, in which T cells recognize processed donor MHC peptides presented in association with self-MHC on recipient antigen presenting cells. We are currently pursuing the dissection of the molecular and cellular mechanisms involved in direct and indirect T cell responses involved in allograft rejection. Based upon this knowledge, we are attempting to design antigen-specific strategies in order to induce tolerance to alloantigens and long-term graft survival in the absence of immunosuppressive treatment.

Area 2: Immunity to cancer In tumor cells, p53 is expressed in mutated form and and in large quantities, in new cell compartments. These properties of p53 make it as an ideal protein first to study immune responses to cancer cells and second to determine whether it is possible to engineer a vaccine against cancer. We have already shown that CD4+ T cell-mediated responses are induced to p53 following tumor formation. Furthermore, we have identified 3 p53 determinants, which elicit CD4+ T cell responses at different stages of tumorigenesis. Based upon this knowledge, we are planning to determine whether these peptides can be utilized to design cancer vaccines.

Papers & Publications:

Hucq, S., Liu, Y., Benichou, G & Dana, MR. Relevance of the direct pathway of sensitization in corneal transplantation is disctated by the graft bed environment. J. Immunol, 2004, 173:4464-9.

Akiyama, Y., Caucheteux, SM., Iwamoto, I., Guimezamnes, Y., Kanellopoulos-Langevin C & Benichou, G. Effects of noninherited maternal antigens on allotransplant rejection in a transgenic mouse model. Transplant
Proc. 2005 37:1940-1.

Bueter, M., Gasser, M., Schramm, N., Lebedeva T, Tocco, G., Gerstlauer, C., Grimm, M., Nichiporuk, E., Thalheimer, A., Thiede, A., Meyer, D., Benichou, G & Waaga-Gasser, AM. T-cell response to p53 tumor-associated antigen in patients with colorectal carcinoma. Int J Oncol. 2006, 28:431-8.

Lechene, C., Cotanche, DA., Benson, D., Bonventre, J., Hillion, F., Hentshel, D., Kampf, P., Kleinfeld, AM., Luyten, Y., Park, KM., Schwartz, M., Benichou, G., Ito, S and Slodzian G. High resolution quantitative imaging of mamalian and bacterial cells using stable isotope mass spectrometry. Jal. of Biology. 2006.

Tocco, G., Illigens, BM., Malfroy, B & Benichou,G. Prolongation of alloskin graft survival by catalytic scavengers of reactive oxygen species. Cell. Immunol. 2006.