Cutting edge: killer Ig-like receptors mediate "missing self" recognition in vivo.
Although it is well established that human NK cells are able to detect the absence of autologous HLA class I in vitro by virtue of inhibitory killer Ig-like receptors (KIR), direct evidence that KIR can mediate "missing self" recognition in vivo is lacking. To test this, we generated mice transgenic for a human KIR B-haplotype and HLA-Cw3 on a C57BL/6 background. NK cells in these mice expressed multiple KIR in a stochastic manner, including the HLA-Cw3-specific inhibitory receptor KIR2DL2. KIR and HLA transgenic mice rejected wild-type C57BL/6 spleen cells upon i.v. injection. This rejection was dependent on the presence of the KIR transgene in the host and on the absence of HLA-Cw3 from the injected target cells. Hence, the KIR transgene mediated "missing self" recognition in vivo. We anticipate that this KIR and HLA transgenic mouse will help shed light on KIR and HLA effects in disease and transplantation.
van Bergen
Jeroen
J
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands. J.van_Bergen@lumc.nl
Thompson
Allan
A
Retière
Christelle
C
Trowsdale
John
J
Koning
Frits
F
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D001324:Autoantigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015236:HLA-C Antigens / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000096:biosynthesis / Q000235:genetics; D054343:Receptors, KIR2DL2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D013269:Stochastic Processes
D001324:Autoantigens; D015236:HLA-C Antigens; C038653:HLA-C*03 antigen; C106548:HLA-C*03:04 antigen; C515077:KIR2DL2 protein, human; D055650:NK Cell Lectin-Like Receptor Subfamily A; D054343:Receptors, KIR2DL2