reviews: update hamerman, j. a., ogasawara, k., lanier, l. l. (2005)
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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. - PowerPoint PPT PresentationTRANSCRIPT
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 ??