KIR acquisition probabilities are independent of self-HLA class I ligands and increase with cellular KIR expression

CD8 T cells express randomly selected KIRs with distinct specificities compared with NK cells

“…Hence, the observed distribution of self-and nonself-KIRs on CD8 T cells was almost identical to the theoretical values of KIR expression expected from a random distribution without any evidence for selection imposed by the presence of cognate ligands ( Figure 5B). In agreement with our previous findings, 16 KIR expression on NK cells in these 24 individuals was also random without any influence by cognate HLA class I molecules ( Figure 5C). Hence, despite the differing KIR repertoires of NK cells and CD8 T cells ( Figure 3F-H), both cell types had random distributions of self-and nonself-KIRs ( Figure 5B-C).…”

“…11 Although there is a minor influence of HLA class I on the expression of specific KIRs on NK cells, 12,13 that seems more prominent in settings of viral infections, 14,15 KIR expression is primarily determined by KIR gene and promoter polymorphisms as well the production of antisense RNAs in a random process that is not subject to any positive or negative selection. 16,17 To preserve self-tolerance in the absence of repertoire selection, NK cells are functionally tuned in an yet not fully understood educational process in which the strength of the interactions between inhibitory KIRs and their cognate HLA class I ligands is one important factor. 18 Other than NK cells, CD4 and CD8 T cells as well as ␥␦ T cells also express KIRs.…”

Maternal uterine NK cell–activating receptor KIR2DS1 enhances placentation

“…Overall frequencies of both KIR2DL1 and KIR2DS1 are dramatically increased in dNK compared with pbNK from the same donor. The number of dNK that coexpress both receptors was somewhat larger than predicted by the product rule (36). How the selective increase of KIRs in dNK specific for HLA-C occurs in the decidual microenvironment is unknown, but it is a response to pregnancy, since it is not seen in nonpregnant endometrium (13).…”

NK cell responses to cytomegalovirus infection lead to stable imprints in the human KIR repertoire and involve activating KIRs

“…49,50 However, there is no evidence for negative selection or deletion of NK cells expressing a combination of receptors that could be harmful or useless. 28 Furthermore, no bias for expression of self-specific KIRs could be detected in another cohort of healthy donors, 51 or in neonates. 52 Potentially explaining the discrepant results in earlier studies, our analysis, including 48 CMV-seronegative donors, shows that NK cells display a random repertoire without any significant influence from cognate HLA class I molecules.…”