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Receptor-ligand analyses define minimal killer cell Ig-like receptor (KIR) in humans

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Abstract

Interactions between inhibitory killer cell immunoglobulin-like receptors (iKIR) and human leukocyte antigen (HLA) class I molecules regulate natural killer (NK) cell responses to eliminate infected and transformed cells while maintaining tolerance to healthy cells. Unlinked polymorphic gene families encode KIR receptors and HLA class I ligands and their independent segregation results in a variable number and type of iKIR + HLA pairs inherited in individuals. The diversity in the co-inheritance of iKIR + HLA pairs and activating KIR (aKIR) genes in 759 unrelated individuals from four ethnic populations was analyzed. Every individual studied inherited a minimum of one iKIR + HLA pair; suggesting that major histocompatibility complex class I-dependent inhibitory KIR signaling is essential for human NK cell function. In contrast, 13.4% of the study group lacked all aKIR genes. Twenty percent of the study group carried only one of the four iKIR + HLA pairs. Interestingly, 3% of the study group carrying only KIR2DL3 + HLA-C1 as an iKIR + HLA pair lacked aKIR genes. These data suggest that a single iKIR can constitute the minimal KIR repertoire for human NK cells. Genotypes carrying an equal number of iKIR + HLA pairs and aKIR genes represented 20% of the study group. The remaining individuals had either a dominant inhibitory KIR genotype (iKIR + HLA > aKIR) or a dominant activating KIR genotype (iKIR + HLA < aKIR). Genotypes encoding these imbalanced inhibitory and activating interactions may contribute to susceptibility or resistance to human diseases.

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Acknowledgment

This work was supported by Stein Oppenheimer Endowment Award and start-up funds from the Department of Pathology and Laboratory Medicine to Dr. Rajalingam. We thank John Muramoto for providing DNA samples from the UCLA International DNA Exchange Program for this study.

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Authors and Affiliations

  1. UCLA Immunogenetics Center, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, 1000 Veteran Avenue, Room No. 1-536, Los Angeles, CA, 90095-1652, USA

    Zeying Du, David W. Gjertson, Elaine F. Reed & Raja Rajalingam

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  1. Zeying Du
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  2. David W. Gjertson
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  3. Elaine F. Reed
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  4. Raja Rajalingam
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Correspondence to Raja Rajalingam.

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Du, Z., Gjertson, D.W., Reed, E.F. et al. Receptor-ligand analyses define minimal killer cell Ig-like receptor (KIR) in humans. Immunogenetics 59, 1–15 (2007). https://doi.org/10.1007/s00251-006-0168-4

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  • DOI: https://doi.org/10.1007/s00251-006-0168-4

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