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John E. Coligan, Ph.D.
Twinbrook II, Room 205
12441 Parklawn Drive, MSC 8180
Rockville, MD 20852-1742
Phone: 301-496-8247
Fax: 301-480-2818
jcoligan@niaid.nih.gov

Laboratory of Immunogenetics

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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, virally infected 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. NKG2D-DAP10 can also be expressed by T lymphocytes and, as such, can facilitate several autoimmune diseases (e.g., celiac disease, rheumatoid arthritis, and diabetes).

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. On the other hand, any down-regulation of inhibitory receptors by NK cells would release their potential for killing normal cells, leading to autoimmunity.

Ongoing studies include the following (see individual investigators for more details):

  • Elucidating the mechanisms for endocytosis, intracellular trafficking, and signal transduction of  NK cell inhibitory receptors
  • Investigating the mechanisms of exocytosis during generation of NK-cell function, with particular focus on regulation of lytic granule fusion and cytoskeletal rearrangements in cytotoxicity of  NK cells
  • Determination of the factors and processes that regulate expression and function of the NKG2D-DAP10 activation receptor
  • Determination of the roles of the LAIR-1 and CD300lf inhibitory receptors in regulating the immune response
  • Understanding the role of TOSO (FAIM-3), an IgM receptor, in regulating the function of NK and T cells

    Receptor Cell Biology group photo

Receptor Cell Biology Section, January 2013 (L-R): Mirna Pena, Linjie Tian, John E. Coligan, Konrad Krzewski, Giovanna Peruzzi, Yousuke Murakami, Seung-Chul Choi, Miri Gitik, Aleksandra Gil-Krzewska

John E. Coligan, Ph.D., Chief
Konrad Krzewski, Ph.D.

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Last Updated December 07, 2009