Detection of KIR3DS1 on the Cell Surface of Peripheral Blood NK Cells Facilitates Identification of a Novel Null Allele and Assessment of KIR3DS1 Expression during HIV-1 Infection

Abstract

KIR3DL1 is a highly polymorphic killer cell Ig-like receptor gene with at least 23 alleles described, including its activating counterpart, KIR3DS1. Recently, the KIR3DS1 allele has been shown to slow progression to AIDS in individuals expressing HLA-Bw4 with isoleucine at position 80. However, due to the lack of a specific Ab, KIR3DS1 expression and function is not well characterized. In this study, we demonstrate KIR3DS1 expression on a substantial subset of peripheral natural killer cells through its recognition by the mAb Z27. The fidelity of this detection method was confirmed by analysis of KIR3DS1 transfectants and the identification of a novel KIR3DS1 null allele. Interestingly, KIR3DS1 is also expressed by a small proportion of CD56+ T cells. We show that ligation of KIR3DS1 by Z27 leads to NK cell IFN-γ production and degranulation as assessed by expression of CD107a. Furthermore, we document the persistence of KIR3DS1+ NK cells in HIV-1 viremic patients. The high frequency of KIR3DS1 expression, along with its ability to activate NK cells, and its maintenance during HIV-1 viremia are consistent with the epidemiological data suggesting a critical role for this receptor in controlling HIV-1 pathogenesis.

Phenotypic and Functional Analyses of KIR3DL1+ and KIR3DS1+ NK Cell Subsets Demonstrate Differential Regulation by Bw4 Molecules and Induced KIR3DS1 Expression on Stimulated NK Cells

“…On the other hand, no significant difference was observed in KIR3DL1 ϩ NK cell frequency according to the presence or absence of the autologous ligand Bw4. The discrepancy between these observations and previous reports (13,32) can potentially be explained by different allelic distributions of KIR3DL1/S1 and HLA-Bw4 between our European cohort and American (32) and Japanese (13) cohorts (47)(48)(49)(50). These data support an influence of HLA-Bw4 molecules in shaping the KIR3DS1 ϩ NK cell subset during development.…”

Influence of KIR gene copy number on natural killer cell education

“…3,5,10 To determine whether such gene dose effects apply to a broader set of For personal use only. on May 11, 2018.…”

HIV Protective KIR3DL1 and HLA-B Genotypes Influence NK Cell Function Following Stimulation with HLA-Devoid Cells

“…However, the fluorescence intensity of Ab binding to the inhibitory versus activating forms of these receptors differs, such that 3DL1 + NK cell (Z27 hi ) and 3DL1 2 NK cell (Z27 dim or Z27 2 ) are readily distinguishable (35,36). All 61 individuals included in this study are 3DL1 hmz.…”