Gordon J. Freeman, PhD

Dana-Farber Cancer Institute

Academic Titles

Professor, Medicine, Harvard Medical School

Research Program Affiliation

Member, Melanoma

Member, Cancer Immunology

Research Abstract

My laboratory studies the role of costimulatory signals in the development of an immune response. T cell activation requires two signals. Specificity is provided by TCR recognition of peptide-MHC complexes but a second, costimulatory signal is required for full T cell activation. The B7 gene family, comprised of B7-1 and B7-2, provide the critical costimulatory signal for full T cell activation, clonal expansion, and development of effector function through their interaction with CD28 on T cells. After T cell activation, the interaction of B7-1 and B7-2 with the higher affinity ligand, CTLA4, expressed on activated T cells, leads to down-regulation of T cell activation. Stimulation of the TCR alone leads to T cell clonal anergy thus blockade of B7-1 and B7-2 can be used to establish antigen-specific tolerance for transplantation or the alleviation of autoimmunity. Conversely, expression of B7-1 and B7-2 can stimulate an immune response and the introduction of B7-1 or B7-2 into tumors can stimulate an anti-tumor response leading to tumor rejection and anti-tumor immunity. Recently, we have cloned two novel members of the B7 gene family. These new B7s bind to receptors expressed on activated T cells and further regulate the development of an immune response. We are currently focusing on the function of these novel B7 genes and their interactions with the B7/CD28-CTLA4 pathway.