Receptor Cell Biology Section
The Receptor Cell Biology Section studies how various receptors serve to regulate immune cell function, with emphasis on natural killer (NK) cells. NK cells are inflammatory cytokine-producing and/or cytotoxic lymphocytes that compose a major component of the innate immune system and are especially responsible for protection against tumorigenisis and viral infection.
NK cells express a large variety of activation receptors that mediate the recognition and destruction of aberrant cells. A prime example is NKG2D/DAP10, which recognizes ligands—MICA/B and UBLPs in humans—that tend to be elevated in expression on tumor cells and other abnormal cells. Many of the ligands recognized by these activation receptors can be expressed by normal cells and, hence, can potentiate autoimmunity. In several known autoimmune diseases (e.g., celiac disease, rheumatoid arthritis, and diabetes), the expression NKG2D/DAP10 by T lymphocytes has been shown to play such a role.
The destructive potential of NK cells is held in check by the expression of a panel of inhibitory receptors. Of prime importance are the KIR and CD94/NKG2A receptors that recognize MHC class I molecules that tend to be expressed by all normal cells. All else being equal, inhibitory receptor signals predominate over activation signals, thereby protecting normal cells from activation receptor-mediated destruction. The tendency for tumor cells and virally infected cells to down-regulate MHC class I molecules makes them vulnerable to NK cell-mediated attack. In addition to the expression of inhibitory receptors, excessive inflammation due to the stimulation of lymphocytes is highly regulated by a variety of other means, including activation-induced cell death (AICD).
Our research interests are focused on aspects of the aforementioned means of regulating NK- and T-lymphocyte function.
Ongoing studies include the folowing:
- Intracellular trafficking and signal transduction in NK cells, with particular emphasis on processes regulating cytolytic function of NK cells
- Understanding the relationship between intracellular trafficking and function of the CD94/NKG2A and other inhibitory receptors, such as LAIR-1, in relation to activation receptors, such as NKG2D
- Determination of the factors and processes that regulate expression and function of the NKG2D/DAP-10 activation receptor
- Determination of the roles of the LAIR-1 and CD300lf inhibitory receptors in regulating the immune response
- Understanding the regulation and function of the anti-apoptotic molecule TOSO (FAIM-3) in regulating the activation-induced cell death (AICD) of NK and T cells
Receptor Cell Biology Section, October 2009: Giovanna Peruzzi, Seung-Chul Choi, Yuk Pheel Park, Mirna Pena, Konrad Krzewski, Robert Valas, Yousuke Murakami, Linjie Tian, Sriram Narayanan, Claudine Jones, John E. Coligan
John E. Coligan, Ph.D., Chief
Konrad Krzewski, Ph.D.
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