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

Palmer, William H.; Leaton, Laura Ann; Codo, Ana Campos; Hume, Patrick S.; Crute, Bergren; Stone, Matthew L.; Bokhoven, Adrie van; Tobin, Richard P.; McCarter, Martin; Janssen, William J.; Roest, James; Zhu, Shiying; Petersen, Jan; Vivian, J.P.; Rossjohn, Jamie; Trowsdale, John; Getahun, Andrew; Cambier, John C.; Loh, Liyen; Norman, Paul J.

doi:10.1101/2022.08.17.503789

Cited by 2 publications

(4 citation statements)

References 120 publications

(172 reference statements)

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“…KIR3DL3 is a polymorphic molecule barely detectable by FACS (27). After screening various cell lines by RT-qPCR followed by FACS analysis using a polyclonal anti-HHLA2 antibody, we did not find a cell line that naturally expresses HHLA2 at the protein level (Supplementary Figure 5A, B).…”

Section: Targeting Cd28h Bypasses Some Inhibitory Signaling Sensed By...mentioning

confidence: 95%

“…CD28H is expressed on T cells, NK cells, ILCs, and pDC (5,8) and it binds to HHLA2's IgV1 domain (7). Demonstrating KIR3DL3 protein expression on T and NK cells is challenging due to its poor to no expression on circulating T and NK cells (4,9) and to difficulties in obtaining reliable antibodies because of homologies between the KIR proteins (4,7,9,10).…”

Section: Introductionmentioning

confidence: 99%

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Correct stimulation of CD28H arms NK cells against tumor cells

HASPOT,

Duplouye,

Leau

et al. 2023

Preprint

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Tumor evasion has recently been associated with a new member of the B7 family, HHLA2, mostly overexpressed on PDL1neg tumors. HHLA2 can either induce a costimulation signal when binding to CD28H or inhibition by binding to KIR3DL3 on T and NK cells. Given the broad distribution of CD28H on NK cells and its depicted role, we compare in this study two monoclonal antibodies targeting this new NK cell engager. We show that targeting CD28H at a specific epitope not only strongly activates Ca2+ flux but also results in NK cell activation. CD28H-activated NK cells further display increased cytotoxic activities against hematopoietic cell lines and bypass HHLA2 and HLA-E inhibitory signals. Additionally, scRNASeq analysis of clear cell kidney cancer cells (ccRCC) reveals that HHLA2+ ccRCC tumors are infiltrated with CD28H+NK cells which thus could be targeted by finely chosen anti-CD28H Abs.

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Section: Targeting Cd28h Bypasses Some Inhibitory Signaling Sensed By...mentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Correct stimulation of CD28H arms NK cells against tumor cells

HASPOT,

Duplouye,

Leau

et al. 2023

Preprint

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“…There are established exceptions and refinements to these broad rules, 51–54 and the full matrix of interactions that were counted is given in the Supplementary Figure 2 of Deng et al 2021 21 . KIR2DL5 and KIR3DL3 are not receptors for HLA class I, 55 with the latter characteristic of tissue‐resident T cells rather than NK cells 56 …”

Section: Methodsmentioning

confidence: 99%

“…21 KIR2DL5 and KIR3DL3 are not receptors for HLA class I, 55 with the latter characteristic of tissue-resident T cells rather than NK cells. 56…”

Section: Hla/kir Interactionsmentioning

confidence: 99%

Exceptional diversity of KIR and HLA class I in Egypt

Montero‐Martin,

Kichula,

Misra

et al. 2023

HLA

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Genetically determined variation of killer cell immunoglobulin like receptors (KIR) and their HLA class I ligands affects multiple aspects of human health. Their extreme diversity is generated through complex interplay of natural selection for pathogen resistance and reproductive health, combined with demographic structure and dispersal. Despite significant importance to multiple health conditions of differential effect across populations, the nature and extent of immunogenetic diversity is under‐studied for many geographic regions. Here, we describe the first high‐resolution analysis of KIR and HLA class I combinatorial diversity in Northern Africa. Analysis of 125 healthy unrelated individuals from Cairo in Egypt yielded 186 KIR alleles arranged in 146 distinct centromeric and 79 distinct telomeric haplotypes. The most frequent haplotypes observed were KIR‐A, encoding two inhibitory receptors specific for HLA‐C, two that are specific for HLA‐A and ‐B, and no activating receptors. Together with 141 alleles of HLA class I, 75 of which encode a KIR ligand, we identified a mean of six distinct interacting pairs of inhibitory KIR and HLA allotypes per individual. We additionally characterize 16 KIR alleles newly identified in the study population. Our findings place Egyptians as one of the most highly diverse populations worldwide, with important implications for transplant matching and studies of immune‐mediated diseases.

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

Cited by 2 publications

References 120 publications

Correct stimulation of CD28H arms NK cells against tumor cells

Correct stimulation of CD28H arms NK cells against tumor cells

Exceptional diversity of KIR and HLA class I in Egypt

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