Cell-Extrinsic MHC Class I Molecule Engagement Augments Human NK Cell Education Programmed by Cell-Intrinsic MHC Class I

Boudreau, Jeanette E.; Liu, Xiaorong; Zhao, Zeguo; Zhang, Aaron; Shultz, Leonard D.; Greiner, Dale L.; Dupont, Bo; Hsu, Katharine C.

doi:10.1016/j.immuni.2016.07.005

Cited by 64 publications

(64 citation statements)

References 45 publications

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“…Although HLA-KIR interactions normally occur in trans, cis interactions have been observed in mice 47,48 . Ly49 receptors have a flexible stalk, which KIR do not, allowing for a cis interaction to take place 49 . Nonetheless, HLA-LILR cis interactions have been shown in humans and therefore cis HLA-KIR interactions cannot be excluded 50,51 .…”

Section: Discussionmentioning

confidence: 99%

Intra-lineage Plasticity and Functional Reprogramming Maintain Natural Killer Cell Repertoire Diversity

Pfefferle

Jacobs

Ask

et al. 2019

Preprint

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One Sentence Summary: High-resolution flow cytometry combined with single-cell RNA sequencing reveal a role for intra-lineage plasticity and functional reprogramming in maintaining phenotypically and functionally diverse NK cell repertoires during IL-15-driven homeostatic proliferation. 2 Abstract Natural killer (NK) cell repertoires are made up of a vast number of phenotypically distinct subsets with different functional properties. The molecular programs involved in maintaining NK cell repertoire diversity under homeostatic conditions remains elusive. Here we show that subsetspecific NK cell proliferation kinetics correlate with mTOR activation, and that global repertoire diversity is maintained through a high degree of intra-lineage subset plasticity during IL-15-driven homeostatic proliferation in vitro. High-resolution flow cytometry and single cell RNA sequencing revealed that slowly cycling sorted KIR + CD56 dim NK cells with an induced CD57 phenotype display increased functional potential associated with inhibitory MHC interactions and activating DAP12 signaling. In contrast, rapidly cycling cells upregulate NKG2A and display a general loss of functionality associated with a transcriptional increase in RNA-binding metabolic enzymes and cytokine signaling pathways. These results shed new light on the role of intra-lineage plasticity during NK cell homeostasis and suggest that the functional fate of the cell is tightly linked to the acquired phenotype and determined by transcriptional reprogramming.

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Section: Discussionmentioning

confidence: 99%

Intra-lineage Plasticity and Functional Reprogramming Maintain Natural Killer Cell Repertoire Diversity

Pfefferle

Jacobs

Ask

et al. 2019

Preprint

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“…Therefore, our data suggested that when donor KIRs were ligated by recipient and donor class I at the same time, IFN-c secretion by reconstituted donor-derived NK cells was enhanced to defend against CMV infection. Boudreau et al (2016) recently demonstrated that NK cell reactivity increased or decreased when HLA was acquired from neighbouring cells or was silenced in educated cells, respectively. In a mouse model, Yokoyama and Kim (2006) demonstrated that NK cells are regulated by the host class I MHC molecules.…”

Section: Discussionmentioning

confidence: 99%

“…However, Sungur et al (2013) have indicated that NK cell licensing corresponds with the donor and not the host MHC haplotype following mismatched allo-HSCT in mice. Boudreau et al (2016) recently demonstrated that NK cell reactivity increased or decreased when HLA was acquired from neighbouring cells or was silenced in educated cells, respectively. Therefore, both cell-intrinsic and -extrinsic HLA cooperate to maintain and adjust NK cell education.…”

Section: Discussionmentioning

confidence: 99%

Recipient‐donor KIR ligand matching prevents CMV reactivation post‐haploidentical T cell‐replete transplantation

Zhao

Luo

et al. 2017

Br J Haematol

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Licensed natural killer (NK) cells have been demonstrated to have anti-cytomegalovirus (CMV) activity. We prospectively analysed the human leucocyte antigen typing of donor-recipient pairs and the killer cell immunoglobulin-like receptor (KIR) typing of donors for 180 leukaemia patients to assess the predictive roles of licensed NK cells on CMV reactivation post-T-cell-replete haploidentical stem cell transplantation. Multivariate analysis showed that donor-recipient KIR ligand graft-versus-host or host-versus-graft direction mismatch was associated with increased refractory CMV infection (Hazard ratio = 2·556, 95% confidence interval, 1·377-4·744, P = 0·003) post-transplantation. Donor-recipient KIR ligand matching decreased CMV reactivation [51·65% (46·67, 56·62%) vs. 75·28% (70·87, 79·69%), P = 0·012], refractory CMV infection [17·58% (13·77, 21·40%) vs. 35·96% (31·09, 40·82%), P = 0·004] and CMV disease [3·30% (1·51, 5·08%) vs. 11·24% (8·04, 14·43%), P = 0·024] by day 100 post-transplantation. In addition, the percentage of γ-interferon expression on donor-derived NK cells was significantly higher in the recipients among the recipient-donor pairs with a KIR ligand match compared with that in the recipients among the pairs with a KIR ligand graft-versus-host or host-versus-graft direction mismatch on days 30 and 100 post-transplantation (P = 0·036 and 0·047, respectively). These findings have suggested that donor-recipient KIR ligand matching might promote the NK cell licensing process, thereby increasing NK cell-mediated protection against CMV reactivation.

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“…212 Using a mouse transgenic for an HLA-B allele that encodes the Bw4 epitope, a recent study investigated the roles of cell-intrinsic and cell-extrinsic HLA class I molecules for educating human NK cells. 213 Because mice and humans are so divergent, primates are used as in vivo models to study NK cell biology. Some non-human simian species show a comparable level of diversity and complexity in KIR haplotypes to humans.…”

Section: Kir Model Systemsmentioning

confidence: 99%

Deciphering the killer‐cell immunoglobulin‐like receptor system at super‐resolution for natural killer and T‐cell biology

et al. 2016

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SummaryKiller‐cell immunoglobulin‐like receptors (KIRs) are components of two fundamental biological systems essential for human health and survival. First, they contribute to host immune responses, both innate and adaptive, through their expression by natural killer cells and T cells. Second, KIR play a key role in regulating placentation, and hence reproductive success. Analogous to the diversity of their human leucocyte antigen class I ligands, KIR are extremely polymorphic. In this review, we describe recent developments, fuelled by methodological advances, that are helping to decipher the KIR system in terms of haplotypes, polymorphisms, expression patterns and their ligand interactions. These developments are delivering deeper insight into the relevance of KIR in immune system function, evolution and disease.

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Cell-Extrinsic MHC Class I Molecule Engagement Augments Human NK Cell Education Programmed by Cell-Intrinsic MHC Class I

Cited by 64 publications

References 45 publications

Intra-lineage Plasticity and Functional Reprogramming Maintain Natural Killer Cell Repertoire Diversity

Intra-lineage Plasticity and Functional Reprogramming Maintain Natural Killer Cell Repertoire Diversity

Recipient‐donor KIR ligand matching prevents CMV reactivation post‐haploidentical T cell‐replete transplantation

Deciphering the killer‐cell immunoglobulin‐like receptor system at super‐resolution for natural killer and T‐cell biology

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