RT Journal Article
SR Electronic
T1 In vitro education of human natural killer cells by KIR3DL1
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201900434
DO 10.26508/lsa.201900434
VO 2
IS 6
A1 Jason Pugh
A1 Neda Nemat-Gorgani
A1 Zakia Djaoud
A1 Lisbeth A Guethlein
A1 Paul J Norman
A1 Peter Parham
YR 2019
UL https://www.life-science-alliance.org/content/2/6/e201900434.abstract
AB During development, NK cells are “educated” to respond aggressively to cells with low surface expression of HLA class I, a hallmark of malignant and infected cells. The mechanism of education involves interactions between inhibitory killer immunoglobulin–like receptors (KIRs) and specific HLA epitopes, but the details of this process are unknown. Because of the genetic diversity of HLA class I genes, most people have NK cells that are incompletely educated, representing an untapped source of human immunity. We demonstrate how mature peripheral KIR3DL1+ human NK cells can be educated in vitro. To accomplish this, we trained NK cells expressing the inhibitory KIR3DL1 receptor by co-culturing them with target cells that expressed its ligand, Bw4+HLA-B. After this training, KIR3DL1+ NK cells increased their inflammatory and lytic responses toward target cells lacking Bw4+HLA-B, as though they had been educated in vivo. By varying the conditions of this basic protocol, we provide mechanistic and translational insights into the process NK cell education.