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 killerCells 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 roleof 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 useof NK cells in immunotherapy of human cancer.Nat. Rev. Immun. 7, 329-339.

Genomic localization

Chr19 LRCChr12 NKC

Recent evolution human - mouse: convergent evolution

Interactions MHC and MHC-like proteins

Polymorphisms

chr

chr

NKR-P1A

200kb

40kb

CLEC-2 CLEC-1DECTIN-1LOX-1 CD94 NKG2D LY49L

The human NKC

Konvergente Evolution:2 unterschiedlicheRezeptorklassenfür gleiche FunktionIn Mensch und Maus

keine funktionellenKIR´s

keine funktionellenLy49

NKG2-D and stress / viral infection / tumors

3 Liganden hochreguliert bei Stress, Virusinfektion, in Tumorzellen:MIC-A, -BRAEsULBPs

CMV immune evasion strategies

HCMV:reguliert MHC class I hinunterUL40 Peptid bringt HLA-E wieder hoch / inhibitive CD94/NKG2A InteraktionUL18 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 LeukozytenMonocyten, 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 expressionin 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 MHCis present

Possibility:first stimulatory receptors,induce expression inhibitoryreceptors until zero sumbetween stimulation andInhibition

Question:NK cells are alloreactivebut self-tolerant, how ??