Abstract

The Cytotoxic Cell Studies Group has made significant advances in our study of members of the murine Ly49 family. The Ly49 repertoire of 129/J mice was investigated by screening a NK cDNA expression library constructed by our lab. Six novel Ly49 cDNAs have been cloned and characterized. An additional novel Ly49 has been isolated from the CBA/J mouse strain. Three of the new Ly49s we have isolated represent novel NK cell activation receptors (Ly49L, Ly49R and Ly49U). We have shown that these activating receptors associate with the DAP-12 signal transduction molecule that is required for the generation of the activation signal. We are currently investigating the MHC class I specificity of the novel receptors. Our studies of the Ly49 promoter structure have led to the identification of an additional upstream promoter. We have cloned several Ly49 intergenic segments, and a comparison of the promoter regions is underway.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010013-05
Application #
6433178
Study Section
(LEI)
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2000
Total Cost
Indirect Cost

  Institution

Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  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
Gosselin, P; Makrigiannis, A P; Nalewaik, R et al. (2000) Characterization of the Ly49I promoter. Immunogenetics 51:326-31
Makrigiannis, A P; Anderson, S K (2000) Ly49 gene expression in different inbred mouse strains. Immunol Res 21:39-47

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