PT  - JOURNAL ARTICLE
AU  - Jason Pugh
AU  - Neda Nemat-Gorgani
AU  - Zakia Djaoud
AU  - Lisbeth A Guethlein
AU  - Paul J Norman
AU  - Peter Parham
TI  - In vitro education of human natural killer cells by KIR3DL1
AID  - 10.26508/lsa.201900434
DP  - 2019 Dec 01
TA  - Life Science Alliance
PG  - e201900434
VI  - 2
IP  - 6
4099  - https://www.life-science-alliance.org/content/2/6/e201900434.short
4100  - https://www.life-science-alliance.org/content/2/6/e201900434.full
SO  - Life Sci. Alliance2019 Dec 01; 2
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.