Immunogenomics of Killer Cell Immunoglobulin-Like Receptor (KIR) and HLA Class I: Coevolution and Consequences for Human Health

Pollock, Nicholas R; Harrison, Genelle F; Norman, Paul J.

doi:10.1016/j.jaip.2022.04.036

Cited by 30 publications

(38 citation statements)

References 251 publications

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“…Polymorphic HLA class I are expressed by most nucleated cells and present intracellular peptides to cytotoxic (CD8+) T cells (Neefjes et al 2011) and therefore are particularly important in the defense against intracellular pathogens, such as viruses. Additionally, some polymorphic HLA class I serve as ligands for NK cell receptors, most notably the killer cell immunoglobulin-like receptors (KIR) (Pollock et al 2022) and leukocyte immunoglobulin-like receptors (LILR) (Brown et al 2004). HLA class I on healthy cells signals "self" through inhibitory NK cell receptors to block NK cell cytotoxicity, but virus-driven HLA downregulation can remove this inhibition, leaving diseased cells vulnerable to NK cell attack (Braud et al 1998;Hansen and Bouvier 2009;Hilton and Parham, 2017;Pazmany et al 1996;Shukla et al 2015).…”

Section: The Arms Of Hla Immunitymentioning

confidence: 99%

The impact of HLA polymorphism on herpesvirus infection and disease

Palmer¹,

Norman²

2023

Immunogenetics

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Human Leukocyte Antigens (HLA) are cell surface molecules, central in coordinating innate and adaptive immune responses, that are targets of strong diversifying natural selection by pathogens. Of these pathogens, human herpesviruses have a uniquely ancient relationship with our species, where coevolution likely has reciprocating impact on HLA and viral genomic diversity. Consistent with this notion, genetic variation at multiple HLA loci is strongly associated with modulating immunity to herpesvirus infection. Here, we synthesize published genetic associations of HLA with herpesvirus infection and disease, both from case/control and genome-wide association studies. We analyze genetic associations across the eight human herpesviruses and identify HLA alleles that are associated with diverse herpesvirus-related phenotypes. We find that whereas most HLA genetic associations are virus- or disease-specific, HLA-A*01 and HLA-A*02 allotypes may be more generally associated with immune susceptibility and control, respectively, across multiple herpesviruses. Connecting genetic association data with functional corroboration, we discuss mechanisms by which diverse HLA and cognate receptor allotypes direct variable immune responses during herpesvirus infection and pathogenesis. Together, this review examines the complexity of HLA-herpesvirus interactions driven by differential T cell and Natural Killer cell immune responses.

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Section: The Arms Of Hla Immunitymentioning

confidence: 99%

The impact of HLA polymorphism on herpesvirus infection and disease

Palmer¹,

Norman²

2023

Immunogenetics

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“…Sequence reads specific to the KIR region were obtained from multiple studies as described 8,21,118 . The sequence reads were aligned to GRCh38 using bwa (v0.7.17) 119 and promoter variants (863 bp upstream of KIR3DL3 start codon) called using samtools mpileup (v1.7) 88 .…”

Section: Population Genetic Analysis Of the Kir3dl3 Promotermentioning

confidence: 99%

“…Detection and elimination of infected or cancerous cells by cytotoxic lymphocytes is vital for survival [1][2][3] . In this role, alongside those in placentation and tissue transplantation [4][5][6][7][8] , killer cell immunoglobulinlike receptors (KIR) modulate the cytotoxic and inflammatory activity of human natural killer (NK) and T cells 9,10 . Inhibitory KIR educate developing NK cells, enabling them to kill malignant or infected cells marked by altered cell surface ligand expression, namely HLA class I molecules 9,10 .…”

Section: Introductionmentioning

confidence: 99%

Polymorphic KIR3DL3 expression modulates tissue-resident and innate-like T cells

Palmer

Leaton

Codo

et al. 2022

Preprint

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Most human killer cell immunoglobulin-like receptors (KIR) are expressed by Natural Killer (NK) cells and recognize HLA class I molecules as ligands. Uniquely, KIR3DL3 is a conserved but polymorphic inhibitory KIR recognizing a B7 family ligand, HHLA2, and is implicated for immune checkpoint targeting. Because the expression profile and biological function of KIR3DL3 remained elusive, we searched extensively for KIR3DL3 transcripts, revealing expression is highly enriched in γδ and CD8+ T cells rather than NK cells. These KIR3DL3 expressing cells are rare in the blood and thymus, but more common in the lungs and digestive tract. High resolution flow cytometry and single cell transcriptomics showed that peripheral blood KIR3DL3+ T cells have an activated transitional memory phenotype and are hypofunctional. The TCR usage is biased towards genes from early rearranged TCR-α variable segments or Vδ1 chains. Whereas we detected no impact of KIR3DL3 polymorphism on ligand binding, variants in the proximal promoter and at residue 86 can reduce expression. Together, we demonstrate that KIR3DL3 is upregulated in response to unconventional T cell stimulation and that individuals may vary in their ability to express KIR3DL3. These results have implications for the personalized targeting of KIR3DL3/HHLA2 checkpoint inhibition.

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“…Thus, expression is essentially at random during development and may express multiple KIR. (11) The extensive genetic polymorphism of KIR receptors and the regulation of their expression in different NK cell clones are essential factors that delineate each individual's innate and adaptive immune response.…”

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confidence: 99%

A straightforward one-step strategy for SARS-CoV-2 diagnosis and screening of variants of concern: a multicentre study

Fontana-Maurell

Motta

Arruda

et al. 2023

Mem. Inst. Oswaldo Cruz

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BACKGROUND Recurrence is a hallmark of ocular toxoplasmosis (OT), and conditions that influence its occurrence remain a challenge. Natural killer cells (NK) are effectors cells whose primary is cytotoxic function against many parasites, including Toxoplasma gondii. Among the NK cell receptors, immunoglobulin-like receptors (KIR) deserve attention due to their high polymorphism.OBJECTIVES This study aimed to analyse the influence of KIR gene polymorphism in the course of OT infection and its association with recurrences after an active episode.METHODS Ninety-six patients from the Ophthalmologic Clinic of the National Institute of Infectology Evandro Chagas were followed for up to five years. After DNA extraction, genotyping of the patients was performed by polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) utilising Luminex equipment for reading. During follow-up, 60.4% had a recurrence.FINDINGS We identified 25 KIR genotypes and found a higher frequency of genotype 1 (31.7%) with worldwide distribution. We note that the KIR2DL2 inhibitor gene and the gene activator KIR2DS2 were more frequent in patients without recurrence. Additionally, we observed that individuals who carry these genes progressed recurrence episodes slowly compared to individuals who do not carry these genes.MAIN CONCLUSIONS The KIR2DL2 and KIR2DS2 are associated as possible protection markers against ocular toxoplasmosis recurrence (OTR).

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Immunogenomics of Killer Cell Immunoglobulin-Like Receptor (KIR) and HLA Class I: Coevolution and Consequences for Human Health

Cited by 30 publications

References 251 publications

The impact of HLA polymorphism on herpesvirus infection and disease

The impact of HLA polymorphism on herpesvirus infection and disease

Polymorphic KIR3DL3 expression modulates tissue-resident and innate-like T cells

A straightforward one-step strategy for SARS-CoV-2 diagnosis and screening of variants of concern: a multicentre study

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