Reviews: update Hamerman, J. A., Ogasawara, K., Lanier, L. L. (2005). NK cells in innate immunity. Curr Opin Immunol 17, 29-35. W.M. Yokoyama and S. Kim.

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Presentation transcript:

Reviews: update Hamerman, J. A., Ogasawara, K., Lanier, L. L. (2005). NK cells in innate immunity. Curr Opin Immunol 17, W.M. Yokoyama and S. Kim (2006). Licensing of natural killer Cells by self-major histocompatibility complex class I. Immunol. Rev. 214, J.G. Sambrook and S. Beck (2007). Evolutionary vignettes of natural killer cell receptors. Curr. Op. Immun E. Tupin, Y. Kinjo and M. Kronenberg (2007). The unique role of natural killer T cells in the response to microorganisms. Nat. Rev. Microbiol. 5, H.-G. Ljunggren and K.-J. Malmberg (2007). Propsects for the use of NK cells in immunotherapy of human cancer. Nat. Rev. Immun. 7,

Genomic localization Chr19 LRC Chr12 NKC Recent evolution human - mouse: convergent evolution Interactions MHC and MHC-like proteins Polymorphisms

chr

The human NKC

Konvergente Evolution: 2 unterschiedliche Rezeptorklassen für gleiche Funktion In Mensch und Maus keine funktionellen KIR´s keine funktionellen Ly49

NKG2-D and stress / viral infection / tumors 3 Liganden hochreguliert bei Stress, Virusinfektion, in Tumorzellen: MIC-A, -B RAEs ULBPs CMV immune evasion strategies

HCMV: reguliert MHC class I hinunter UL40 Peptid bringt HLA-E wieder hoch / inhibitive CD94/NKG2A Interaktion UL18 ist MHC class I mimic / KIR Interaktion

HCMV: UL16 inhibiert ULBP und MIC Interaktion mit NKG2D

Some new concepts: NK cells and dendritic cells NK/T cells NK cells and tumors Acquisition of receptor repertoire

„NK“ receptors on T lymphocytes and other cell types KIR und CD94/NKG2A /NKG2C: nur NK cells und Subpopulations von NKT cells ILT, LAIR, NKG2D: auch auf anderen Leukozyten Monocyten, Makrophagen, dendritischen Zellen, B Zellen

Acquisition of receptor repertoire Hypothesis: NK cell education (not really understood) each NK cell has several inhibitory and activating receptors, developing NK cell initiates inhibitory receptor gene expression in a sequential, cumulative and stochastic fashion class I deficient mice: NK cells are tolerant „at least one“ hypothesis: formation of repertoire regulated such that „at least one“ inhibitory receptor for one or another self MHC is present

Possibility: first stimulatory receptors, induce expression inhibitory receptors until zero sum between stimulation and Inhibition Question: NK cells are alloreactive but self-tolerant, how ??