Massachusetts General Hospital
Dept. of Surgery, WHT 535
55 Fruit St.
Boston, MA 02114
Fellows currently in my laboratory:
Dr. Georges Tocco - Investigator
Dr. Ogjenka Nadazdin - Instructor
Dr. Cavit Doga Kant - Posdoctoral Fellow
Dr. Makoto Tonsho - Posdoctoral Fellow
Dr. Yohei Yamada - Posdoctoral Fellow
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 transplant 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 leading to 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 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.
Illigens, B., Yamada, A., Anosova, A., Dong, V.M., Sayegh, M.H & Benichou, G. Dual effects of Th1 and Th2 mediated indirect alloresponses on acute and chronic rejection of allotransplants. Eur. J. Immunol, 2009, 9:105-116 (PMID: PMC19658090)
Nadazdin, O., Boskovic, S., Murakami, T., O’Connor, D., Wiseman, R.W., karl, J., Tusher, J.J., Sachs, D.H., Madsen, J.C., Tocoo, G., Kawai, T., Cosimi, A.B & Benichou, G.
Phenotype, distribution and alloreactive properties of memory T cells from cynomolgus monkeys. Am. J. Transplant, 2010, 10:1375-84 (PMID: PMC20486921)
LeGuern, C., Akiyama, Y., Germana, S., Tanaka, K., Fernandez, L., Iwamoto, Y., Houser, S & Benichou, G
Intracellular MHC Class II Controls Regulatory Tolerance to Allogeneic Transplants. J. Immunol, 2010, 184:2394-00
Akiyama, Y., Caucheteux, S., Vernochet, C., Iwamoto, Y., Tanaka, K., Kanellopoulos, C & Benichou, G. Transplantation tolerance to a single non-inherited MHC class I maternal alloantigen studied in a TCR-transgenic mouse model. J. Immunol, 2011, 186:1442-9 (PMID: PMC21178009).
Nadazdin O, Boskovic S, Murakami T, Tocco G, Smith RN, Colvin RB, Sachs DH, Allan J, Madsen JC, Kawai T, Cosimi AB & Benichou G.
Host alloreactive memory T cells influence tolerance to kidney allografts in non-human primates. Science TM, 2011, In press
Last Update: 1/6/2014