Training:
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B.S., 1981: Michigan State University
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Ph.D., 1993: University of Massachusetts Medical Center
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PostDoctoral, 1993-1998: National Institutes of Health Summary of research:
We study the host's innate antiviral and antitumor immune responses mediated through CD1d/NKT cell interactions. Description and summary of research focus of the laboratory:
We study the host's innate antiviral and antitumor immune responses mediated through CD1d/NKT cell interactions. In our laboratory, we study the CD1d molecule, a cell surface glycoprotein that is structurally related to the major histocompatibility complex (MHC) class I molecules. We have previously found that, unlike MHC class I molecules that present peptides to T cells, a major natural ligand of CD1d molecules is the normal cellular glycolipid, glycosylphosphatidylinositol. We have also previously reported that CD1d molecules are recognized by a unique subpopulation of T cells called NKT cells. Recent work in our laboratory has investigated the intracellular trafficking of CD1d molecules and the intracellular processing requirements necessary for glycolipids to become bound to and presented by CD1d molecules for recognition by NKT cells. We have found that the processing of CD1d-presented glycolipid antigens occurs in a compartment(s) of the endocytic pathway (e.g., endosomes; lysosomes). We are also investigating the role of CD1d molecules and NKT cells in virus infections. A selective loss of NKT cells from the liver and other organs occurs following infection with several different viruses. We believe that this is a protective mechanism--it has been shown that NKT cells can mediate the destruction of liver tissue upon their activation, such as that which occurs following T cell receptor engagement. We are also interested in the role of NKT cells in antitumor immunity. Our recent work has found evidence that shedding of glycolipids by some tumors can inhibit CD1d-mediated antigen presentation to NKT cells. Current studies are analyzing additional mechanisms by which some tumors can evade this arm of the host's innate antitumor defenses. Publications
Roberts, T. J., Sriram, V., Spence, P. M., Gui, M., Hayakawa, K., Bacik, I., Bennink, J. R., Yewdell, J. W., Brutkiewicz, R. R. Recycling CD1d1 molecules present endogenous antigens processed in an endocytic compartment to NKT cells. J. Immunol. 168:5409-5414, 2002. Sriram, V., Cho, S. Y., Li, P., O'Donnell, P. W., Dunn, C., Hayakawa, K., Blum, J. S., Brutkiewicz, R. R. Inhibition of glycolipid shedding rescues recognition of a CD1 + T cell lymphoma by natural killer T cells. Proc. Natl. Acad. Sci. U.S.A. 99:8197-8202, 2002. Stanic, A. K., De Silva, A. D., Sriram, V., Ichikawa, S., Hirabayashi, Y., Van Kaer, L., Hayakawa, K., Brutkiewicz, R. R ., Joyce, S. Defective presentation of the CD1d1-restricted natural Va14Ja15 NKT lymphocyte antigen caused by b-D-glucosylceramide synthase deficiency. Proc. Natl. Acad. Sci. U.S.A. 100:1849-1854, 2003. Lin, Y., Roberts, T. J., Sriram, V., Cho, S., Brutkiewicz, R. R. Myeloid marker expression on antiviral CD8 + T cells following an acute virus infection. Eur. J. Immunol. 33:2736-2743, 2003. Roberts, T. J., Lin, Y., Spence, P. M., Van Kaer, L., Brutkiewicz, R. R. CD1d1-dependent control of the magnitude of an acute antiviral immune response. J. Immunol. 172:3454-3461, 2004. Search Pub Med Return to Homepage
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