Molecular Studies of Cellular Cytotoxicity

Anderson, Stephen K.

Abstract

The Cytotoxic Cell Studies Group has made significant advances in our study of members of the murine Ly-49 family. Several novel Ly-49 cDNAs isolated from the 129 mouse strain have been cloned and characterized. An additional novel Ly-49 has been isolated from the CBA mouse strain. Two of the new Ly-49s we have isolated represent novel NK cell activation receptors (Ly-49P and Ly-49L). We have shown that these activating receptors associate with a novel signal transduction molecule (DAP-12) that is required for the generation of the activation signal. We have also completed a study linking STAT proteins to the induction of perforin gene transcription by cytokines in NK cells. The regulatory region of the human perforin gene was cloned and used to identify an STAT-binding element that is important for perforin promoter activity. Current studies are directed towards identifying additional molecules involved in the NK cell activation pathway. - Cytotoxicity, Gene regulation, immune response, Natural killer cells, receptors,

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Cancer Institute (NCI)
• Type: Intramural Research (Z01)
• Project #: 1Z01BC010013-04
• Application #: 6289287
• Study Section: Special Emphasis Panel (LEI)
• Support Year: 4
• Fiscal Year: 1999

Institution

• Name: National Cancer Institute Division of Basic Sciences
• Country: United States

Publications

Belanger, S; Tai, L-H; Anderson, S K et al. (2008) Ly49 cluster sequence analysis in a mouse model of diabetes: an expanded repertoire of activating receptors in the NOD genome. Genes Immun 9:509-21

Anderson, S K (2006) Transcriptional regulation of NK cell receptors. Curr Top Microbiol Immunol 298:59-75

Makrigiannis, A P; Patel, D; Goulet, M-L et al. (2005) Direct sequence comparison of two divergent class I MHC natural killer cell receptor haplotypes. Genes Immun 6:71-83

Anderson, S K; Dewar, K; Goulet, M-L et al. (2005) Complete elucidation of a minimal class I MHC natural killer cell receptor haplotype. Genes Immun 6:481-92

Saleh, Ali; Davies, Gareth E; Pascal, Veronique et al. (2004) Identification of probabilistic transcriptional switches in the Ly49 gene cluster: a eukaryotic mechanism for selective gene activation. Immunity 21:55-66

Makrigiannis, Andrew P; Rousselle, Etienne; Anderson, Stephen K (2004) Independent control of Ly49g alleles: implications for NK cell repertoire selection and tumor cell killing. J Immunol 172:1414-25

Makrigiannis, Andrew P; Anderson, Stephen K (2003) Regulation of natural killer cell function. Cancer Biol Ther 2:610-6

Mason, Llewellyn H; Willette-Brown, Jami; Anderson, Stephen K et al. (2003) Receptor glycosylation regulates Ly-49 binding to MHC class I. J Immunol 171:4235-42

Makrigiannis, A P; Anderson, S K (2000) Ly49 gene expression in different inbred mouse strains. Immunol Res 21:39-47

Makrigiannis, A P; Etzler, J; Winkler-Pickett, R et al. (2000) Identification of the Ly49L protein: evidence for activating counterparts to inhibitory Ly49 proteins. J Leukoc Biol 68:765-71