Abstract

The Cytotoxic Cell Studies Group has made significant advances in our study of the murine Ly49 gene family. Our laboratory has identified eight novel Ly49 genes in the 129/J mouse strain. We have constructed a bacterial artificial chromosome (BAC) contig map of the 129/J Ly49 gene cluster, and it demonstrates significant differences in the gene number and organization as compared to B6 mice. The number and type of human killer cell inhibitory receptor (KIR) genes is also highly variable, therefore this finding establishes another parallel between the murine Ly49s and the human KIR family of class I MHC receptors and reinforces the study of the Ly49 system as a model for human KIR function. We have investigated the MHC class I specificity of the novel Ly49 receptors and shown that Ly49 alleles can possess very different patterns of class I MHC recognition. Our studies of the Ly49 promoter structure have led to the identification of an additional upstream promoter that is active early in NK cell differentiation. We have characterized the early promoters of several Ly49 genes and the importance of the early promoter in selective Ly49 gene activation is currently under investigation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010013-06
Application #
6559090
Study Section
(LEI)
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2001
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

Showing the most recent 10 out of 15 publications