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Specificity and function of NK cells: interplay between HLA class I and KIR gene polymorphism

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Host: Ashley Moffett (

Dr. Uhrberg is working in the field of natural killer cell biology. He was the first to describe the polymorphism of the KIR gene family and to develop DNA - as well as RNA -based KIR typing protocols(1). Later on, he discovered the epigenetic regulation of KIR gene expression by DNA methylation and histone modifications as well as the reactivation of silenced KIR genes by epigenetic drugs(2, 3). Dr. Uhrberg runs an internationally accredited immunogenetics facility (ASHI-approved SOP for KIR typing) and is reference laboratory of the International KIR exchange program organized by UCLA since 2004. Recently, the group developed multiparameter flow cytometry techniques to analyze the functional NK cell repertoire on the clonal level, and in combination with either markers for degranulation (CD107), cytokine production (IFNy), or components of the lytic machinery (granzyme B, perforin) to assess the mechanisms that lead to structural and functional education of NK cell repertoires(4)


1. Uhrberg, M., N. M. Valiante, B. P. Shum, H. G. Shilling, K. Lienert-Weidenbach, B. Corliss, D. Tyan, L. L. Lanier, and P. Parham. 1997. Human diversity in killer cell inhibitory receptor genes. Immunity 7:753-763. 2. Santourlidis, S., H. I. Trompeter, S. Weinhold, B. Eisermann, K. L. Meyer, P. Wernet, and M. Uhrberg. 2002. Crucial role of DNA methylation in determination of clonally distributed killer cell Ig-like receptor expression patterns in NK cells. J Immunol 169:4253-4261. 3. Santourlidis, S., N. Graffmann, J. Christ, and M. Uhrberg. 2008. Lineage-specific transition of histone signatures in the killer cell Ig-like receptor locus from hematopoietic progenitor to NK cells. J Immunol 180:418-425. 4. Schönberg, K., M. Sribar, J. Enczmann, J. C. Fischer, and M. Uhrberg. Analyses of HLA -C-specific KIR repertoires in donors with group A and B haplotypes suggest a ligand-instructed model of NK cell receptor aquisition. Blood, in press.

This talk is part of the Immunology in Pathology series.

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