Reviews update Hamerman J A Ogasawara K Lanier

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 (2006). Licensing of natural killer Cells by self-major histocompatibility complex class I. Immunol. Rev. 214, 143 -154. J. G. Sambrook and S. Beck (2007). Evolutionary vignettes of natural killer cell receptors. Curr. Op. Immun. 19. 553 -560 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, 405 -417. H. -G. Ljunggren and K. -J. Malmberg (2007). Propsects for the use of NK cells in immunotherapy of human cancer. Nat. Rev. Immun. 7, 329 -339.

Genomic localization Chr 19 LRC Chr 12 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 Ly 49

NKG 2 -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 UL 40 Peptid bringt HLA-E wieder hoch / inhibitive CD 94/NKG 2 A Interaktion UL 18 ist MHC class I mimic / KIR Interaktion

HCMV: UL 16 inhibiert ULBP und MIC Interaktion mit NKG 2 D

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 CD 94/NKG 2 A /NKG 2 C: nur NK cells und Subpopulations von NKT cells ILT, LAIR, NKG 2 D: 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 ? ?