Publications by authors named "John Trowsdale"

The COVID-19 pandemic highlighted the clear risk that zoonotic viruses pose to global health and economies. The scientific community responded by developing several efficacious vaccines which were expedited by the global need for vaccines. The emergence of SARS-CoV-2 breakthrough infections highlights the need for additional vaccine modalities to provide stronger, long-lived protective immunity.

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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. KIR3DL3 is a conserved but polymorphic inhibitory KIR recognizing a B7 family ligand, HHLA2, and is implicated for immune checkpoint targeting. The expression profile and biological function of KIR3DL3 have been somewhat elusive, so we searched extensively for KIR3DL3 transcripts, revealing highly enriched expression in γδ and CD8 T cells rather than NK cells.

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The biological processes underlying NK cell alloreactivity in haematopoietic stem cell transplantation (HSCT) remain unclear. Many different models to predict NK alloreactivity through KIR and MHC genotyping exist, raising ambiguities in its utility and application for clinicians. We assessed 27 predictive models, broadly divided into six categories of alloreactivity prediction: ligand-ligand, receptor-ligand, educational, KIR haplotype-based, KIR matching and KIR allelic polymorphism.

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Allogeneic hematopoietic stem cell transplantation (aHSCT) is a lifesaving therapy for hematological malignancies. For years, a fully matched HLA donor was a requisite for the procedure. However, new immunosuppressive strategies have enabled the recruitment of viable alternative donors, particularly haploidentical donors.

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Killer immunoglobulin-like receptors (KIRs) are a family of receptors expressed on Natural killer (NK) cells. The extensive polymorphism of KIR is involved in the immune responses of NK cells and influences dengue infections. We investigated the diversity of KIR copy numbers in dengue-infected patients from northeastern Thailand.

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Sialic acid-binding immunoglobulin-like lectin (Siglec)-15 has recently been identified as a critical tumour checkpoint, augmenting the expression and function of programmed death-ligand 1. We raised a monoclonal antibody, A9E8, specific for Siglec-15 using phage display. A9E8 stained myeloid leukaemia cell lines and peripheral cluster of differentiation (CD)33 blasts and CD34 leukaemia stem cells from patients with acute myeloid leukaemia (AML).

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Background: Malaria is one of the most serious infectious diseases in the world. The malaria burden is greatly affected by human immunity, and immune responses vary between populations. Genetic diversity in KIR and HLA-C genes, which are important in immunity to infectious diseases, is likely to play a role in this heterogeneity.

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Objective: In some individuals, coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection leads to a variety of serious inflammatory symptoms, including blood clotting and acute respiratory distress. Death due to COVID-19 shows a steep rise in relation to age. Comorbidities such as type 2 diabetes mellitus (T2DM), hypertension, and cardiovascular disease also increase susceptibility.

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Despite advances in identifying the key immunoregulatory roles of many of the human leukocyte immunoglobulin-like receptor (LILR) family members, the function of the inhibitory molecule LILRB3 (ILT5, CD85a, LIR3) remains unclear. Studies indicate a predominant myeloid expression; however, high homology within the LILR family and a relative paucity of reagents have hindered progress toward identifying the function of this receptor. To investigate its function and potential immunomodulatory capacity, a panel of LILRB3-specific monoclonal antibodies (mAbs) was generated.

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Malaria is one of the deadliest infectious diseases in the world. Immune responses to Plasmodium falciparum malaria vary among individuals and between populations. Human genetic variation in immune system genes is likely to play a role in this heterogeneity.

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Natural killer (NK) cells are innate lymphocytes that eliminate infected and transformed cells. They discriminate healthy from diseased tissue through killer cell Ig-like receptor (KIR) recognition of HLA class I ligands. Directly impacting NK cell function, polymorphism associates with infection control and multiple autoimmune and pregnancy syndromes.

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These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells.

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Killer cell immunoglobulin-like receptors (KIRs) are expressed predominantly on natural killer cells, where they play a key role in the regulation of innate immune responses. Recent studies show that inhibitory KIRs can also affect adaptive T cell-mediated immunity. In mice and in human T cells in vitro, inhibitory KIR ligation enhanced CD8 T cell survival.

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The goals of the KIR component of the 17th International HLA and Immunogenetics Workshop (IHIW) were to encourage and educate researchers to begin analyzing KIR at allelic resolution, and to survey the nature and extent of KIR allelic diversity across human populations. To represent worldwide diversity, we analyzed 1269 individuals from ten populations, focusing on the most polymorphic KIR genes, which express receptors having three immunoglobulin (Ig)-like domains (KIR3DL1/S1, KIR3DL2 and KIR3DL3). We identified 13 novel alleles of KIR3DL1/S1, 13 of KIR3DL2 and 18 of KIR3DL3.

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Killer-cell Ig-like receptor (KIR) genes are inherited as haplotypes. They are expressed by NK cells and linked to outcomes of infectious diseases and pregnancy in humans. Understanding how genotype relates to phenotype is difficult because of the extensive diversity of the KIR family.

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Immune response to disease requires coordinated expression of an army of molecules. The highly polymorphic MHC class I and class II molecules are key to control of specificity of antigen presentation. Processing of the antigen, to peptides or other moieties, requires other sets of molecules.

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Activation of human Vγ9/Vδ2 T cells by "phosphoantigens" (pAg), the microbial metabolite ()-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP) and the endogenous isoprenoid intermediate isopentenyl pyrophosphate, requires expression of butyrophilin BTN3A molecules by presenting cells. However, the precise mechanism of activation of Vγ9/Vδ2 T cells by BTN3A molecules remains elusive. It is not clear what conformation of the three BTN3A isoforms transmits activation signals nor how externally delivered pAg accesses the cytosolic B30.

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KIR (Killer Immunoglobulin-like Receptor) variants influence immune responses and are genetic factors in disease susceptibility. Using sequence-specific priming PCR, we have previously described the diversity of KIR genes in term of presence/absence in northeastern Thais (NETs). To provide additional resolution beyond conventional methods, quantitative PCR was applied to determine KIR copy number profiles.

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The MHC controls specificity, to ensure that appropriate immune responses are mounted to invading pathogens whilst maintaining tolerance to the host. It encodes molecules that act as sentinels, providing a snapshot of the health of the interior and exterior of the cell for immune surveillance. To maintain the ability to respond appropriately to any disease requires a delicate balance of expression and function, and many subtleties of the system have been described at the gene, individual and population level.

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The interaction of inhibitory killer cell Ig-like receptors (KIRs) with human leukocyte antigen (HLA) class I molecules has been characterized in detail. By contrast, activating members of the KIR family, although closely related to inhibitory KIRs, appear to interact weakly, if at all, with HLA class I. KIR2DS1 is the best studied activating KIR and it interacts with C2 group HLA-C (C2-HLA-C) in some assays, but not as strongly as KIR2DL1.

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The human cytomegalovirus (HCMV) US12 family consists of ten sequentially arranged genes (US12-21) with poorly characterized function. We now identify novel natural killer (NK) cell evasion functions for four members: US12, US14, US18 and US20. Using a systematic multiplexed proteomics approach to quantify ~1300 cell surface and ~7200 whole cell proteins, we demonstrate that the US12 family selectively targets plasma membrane proteins and plays key roles in regulating NK ligands, adhesion molecules and cytokine receptors.

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NK cells, which are highly enriched in the liver, are potent regulators of antiviral T cells and immunopathology in persistent viral infection. We investigated the role of the NKG2D axis in T cell/NK cell interactions in hepatitis B. Activated and hepatitis B virus (HBV)-specific T cells, particularly the CD4 fraction, expressed NKG2D ligands (NKG2DL), which were not found on T cells from healthy controls (p < 0.

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The killer cell immunoglobulin-like receptors (KIR) mediate human natural killer (NK) cell cytotoxicity via activating or inhibiting signals. Although informative and functional haplotype patterns have been reported, most genotyping has been performed at resolutions that are structurally ambiguous. In order to leverage structural information given low-resolution genotypes, we performed experiments to quantify the effects of population variations, reference haplotypes, and genotyping resolutions on population-level haplotype frequency estimations as well as predictions of individual haplotypes.

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