Research Interests
Upon exposure to pathogens and other danger signals, the immune system is activated to carry out complex protective responses. In contrast, when there is no stimulation from danger signals, a state of immunological tolerance is maintained. It is now becoming apparent that immunological tolerance is not simply a state of quiescence, but is probably due to active processes that are continually carried out by a variety of regulatory cell types.
My lab studies a population of regulatory T lymphocytes called NKT cells. Whereas most T cells recognize peptide antigens that derive from non-self proteins and are presented at the cell surface by MHC molecules, NKT cells are activated by lipid and glycolipid antigens presented by CD1d molecules. What particularly interests us about NKT cells is that they can become activated by self lipids, which means that they can perform functions even when there is no infectious challenge. The central focus of my lab is to understand how this autoreactivity contributes to immune regulation.
On-going projects in my lab include the following:
- Investigation of how molecular specificity for self and foreign lipid antigens is determined by the T cell receptors (TCRs) of NKT cells.
- Analysis of intracellular signaling events and cell biological processes during NKT cell activation by self and foreign lipids.
- Identification and characterization of self antigens recognized by human NKT cells.
- We have recently demonstrated that human NKT cells direct peripheral blood monocytes to differentiate into immature dendritic cells (DCs). Hence, a current effort is to characterize the down-stream immunological functions of the resulting DCs.
- Development of SCID mouse model systems to investigate the interactions of human NKT cells with monocytes, and the properties of the resulting DCs, in vivo.
Training
1986, B.A., University of California at Santa Cruz, Santa Cruz, CA
1996, Ph.D., Stanford University, Stanford, CA
1996-1999, Research Fellow, Harvard Medical School, Boston, MA
Recent publications NCBI PubMed search for "J. Gumperz"
Chen X, Wang X, Keaton JM, Reddington F, Illarionov PA, Besra GS, Gumperz JE. Distinct endosomal trafficking requirements for presentation of auto-antigens and exogenous lipids by human CD1d molecules. Journal of Immunology. 2007; 178(10):6181-90.
Yuan W, Qi X, Tsang P, Kang SJ, Illarionov PA, Besra GS, Gumperz J, Cresswell P. Saposin B is the dominant saposin that facilitates lipid binding to human CD1d molecules. PNAS. 2007; 104(13):5551-6.
Hegde S, Chen X, Keaton JM, Reddington F, Besra GS, Gumperz JE. NKT cells direct monocytes into a DC differentiation pathway. Journal of Leukocyte Biology. 2007; 81(5):1224-35.
Kim PJ, Pai SY, Brigl M, Besra GS, Gumperz J, Ho IC. GATA-3 regulates the development and function of invariant NKT cells. Journal of Immunology. 2006; 177(10):6650-9.
Brigl M, van den Elzen P, Chen X, Hartt Meyers J, Wu D, Wong C-H, Reddington F, Illarianov P, Besra GS, Brenner MB, Gumperz JE. Conserved and Heterogeneous Lipid Antigen Specificities of CD1d-restricted NKT Cell Receptors. Journal of Immunology. 2006; 176(6):3625-34.
van den Elzen P, Garg S, Brigl M, Gumperz J, Sacks F, Besra GS, Kent SC, Moody DB, Brenner MB. Apolipoprotein-mediated pathways of lipid antigen presentation. Nature. 2005; 437(7060):906-10
Sanchez DJ, Gumperz JE, Ganem D. Regulation of CD1d expression and function by a herpesvirus infection. Journal of Clinical Investigation. 2005; 115(5):1369-78.
Van Rhijn I, Young DC, Im JS, Levery SB, Illarionov PA, Besra GS, Porcelli SA, Gumperz J, Cheng TY, Moody DB. CD1d-restricted T cell activation by nonlipidic small molecules. PNAS. 2004; 101(37):13578-83
Brigl M, Bry L, Kent SC, Gumperz JE*, Brenner MB*. Mechanism of CD1d-restricted Natural Killer T cell activation during microbial infection. Nature Immunology. 2003; 4(12):1230-1237 *These authors contributed equivalently.