PMID- 19693090
OWN - NLM
STAT- MEDLINE
DCOM- 20100323
LR  - 20220317
IS  - 1476-5470 (Electronic)
IS  - 1466-4879 (Linking)
VI  - 11
IP  - 1
DP  - 2010 Jan
TI  - Receptor systems controlling natural killer cell function are genetically 
      stratified in Europe.
PG  - 67-78
LID - 10.1038/gene.2009.60 [doi]
AB  - Natural killer (NK) cells are components of the innate immune system that 
      function in identifying and destroying aberrant or pathogen-infected cells. These 
      functions are largely controlled by killer cell immunoglobulin-like receptors 
      (KIRs). KIRs inhibit and activate NK cell functions through interactions with 
      their ligands, epitopes encoded by human leukocyte antigen (HLA) class I genes 
      (HLA-C1, C2 and Bw4). Genes that encode KIR and their HLA ligands vary in 
      frequency across human populations. Here, we characterize two Irish populations 
      for KIR and HLA and determine the spatial distribution of functionally important 
      KIR:HLA systems in Europe, a region known for its considerable underlying genetic 
      stratification. We find that Southern Europe is a region characterized by higher 
      frequencies of activatory KIR and strong inhibitory HLA ligand systems 
      (2DL1:HLA-C2 and 3DL1:Bw4). A lower frequency of activatory KIR and the 
      predominance of a comparatively weaker inhibitory ligand system (2DL3:HLA-C1) are 
      observed northwards. Despite contrasting KIR:HLA systems in Northern and Southern 
      Europe, there is a clear balance between inhibitory and activatory repertoires, 
      and their ligands in both regions. These findings show 'functional 
      stratification' of the epistatic KIR:HLA receptor system in Europe, the presence 
      of which will likely affect NK cell-mediated immunity across different 
      populations.
FAU - Guinan, K J
AU  - Guinan KJ
AD  - School of Biochemistry and Immunology, Trinity College, Dublin, Ireland.
FAU - Cunningham, R T
AU  - Cunningham RT
FAU - Meenagh, A
AU  - Meenagh A
FAU - Dring, M M
AU  - Dring MM
FAU - Middleton, D
AU  - Middleton D
FAU - Gardiner, C M
AU  - Gardiner CM
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20090820
PL  - England
TA  - Genes Immun
JT  - Genes and immunity
JID - 100953417
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-Bw4 antigen)
RN  - 0 (HLA-C Antigens)
RN  - 0 (Receptors, KIR)
SB  - IM
MH  - Epistasis, Genetic/*genetics/immunology
MH  - Female
MH  - HLA-B Antigens/*genetics/immunology
MH  - HLA-C Antigens/*genetics/immunology
MH  - Humans
MH  - Immunity, Cellular/genetics/immunology
MH  - *Killer Cells, Natural
MH  - Male
MH  - Receptors, KIR/*genetics/immunology
EDAT- 2009/08/21 09:00
MHDA- 2010/03/24 06:00
CRDT- 2009/08/21 09:00
PHST- 2009/08/21 09:00 [entrez]
PHST- 2009/08/21 09:00 [pubmed]
PHST- 2010/03/24 06:00 [medline]
AID - gene200960 [pii]
AID - 10.1038/gene.2009.60 [doi]
PST - ppublish
SO  - Genes Immun. 2010 Jan;11(1):67-78. doi: 10.1038/gene.2009.60. Epub 2009 Aug 20.