Microbiology and Molecular Genetics Michigan State University
2215 Biomedical Physical Sciences East Lansing, MI 48824-4320
Undergrad and Grad Info:
B.S./ M.S., Seoul National University (South Korea)
Ph.D., Mt. Sinai Medical Center, City University of New York
Postdoctoral Fellow / Instructor, Washington University
Department of Microbiology and Molecular Genetics
5198 Biomedical Physical Sciences
Michigan State University
East Lansing, MI 48824MSU
Research Our laboratory is interested in the development and function of natural killer (NK) cells, a subset of lymphocytes that represent a crucial component of the innate immune system. NK cells have the intrinsic ability to efficiently kill diseased cells (e.g., tumor cells and virus-infected cells) and to produce abundant cytokines without the need of prior sensitization. Through these potent effector functions, NK cells contribute significantly to host defense against malignancy and pathogen infection.
To prevent potentially harmful reactivity against normal self-tissues in the body, NK cells must be tightly regulated. Target cell discrimination by NK cells is guided primarily by NK cell surface receptors that recognize polymorphic MHC class I molecules. These receptors display distinctive specificities for different MHC class I alleles, and are expressed in a stochastic manner; thus, NK cells can express either one, more than one or no receptor at al.
Recently, by using transgenic approaches, we have found that only a subpopulation of NK cells are functionally competent in mice and these NK cells (termed ‘licensed' NK cells; see the cartoon below) are the ones that express receptors specific for host (self)-MHC class I. How is it, then, that these licensed NK cells do not attack normal cells? Paradoxically, these MHC-recognizing receptors have also been shown to inhibit NK cell effector functions if the target cells express the appropriate MHC class I molecules. Thus, licensed NK cells can be tolerant to self-tissues through the inhibitory interaction between the receptors and MHC class I molecules that are expressed by all normal cells. Collectively, NK cell tolerance appears to be achieved by the dual (and apparently opposing) roles of the same MHC-recognizing receptors.
Currently, our research is focused on dissecting the molecular mechanisms underlying this licensing process using various gene transfer approaches as well as knockout mouse models. We are also pursuing a better understanding of NK cell development and function in humans.
Yokoyama WM, Kim S. (2006). How do natural killer cells find self to achieve tolerance? Immunity 24:249-257.
Kim S, Poursine-Laurent J, Truscott SM, Lybarger L, Song Y-J, Yang L, French AR, Sunwoo JB, Lemieux S, Hansen TH, Yokoyama WM. (2005). Licensing of natural killer cells by host MHC class I. Nature 436:709-713.
Yokoyama WM, Kim S, French AR. (2004). The dynamic life of natural killer cells. Annu. Rev. Immunol. 22:405-429.
Kim S, Iizuka K, Kang HS, Dokun A, French AR, Greco S, Yokoyama WM. (2002). In vivo developmental stages in murine natural killer cell maturation. Nature Immunol. 3:523-528
Kim S, Iizuka K, Aguila HL, Weissman IL, Yokoyama WM. (2000). In vivo natural killer cell activities revealed by natural killer cell-deficient mice. Proc Natl Acad Sci USA. 97:2731-2736.
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