Development of a novel Haemabiome tool for the high-throughput analysis of haemopathogen species co-infections in African livestock.

One of the principal limitations on livestock productivity in sub-Saharan Africa is the constraining effect of infectious diseases, including tick-borne blood pathogens. Currently, diagnostic markers for these pathogens are species or genus specific, making it challenging to implement high-throughput screening methods. The aim of this study was to develop and validate a novel high-throughput diagnostic tool capable of detecting a range of important haemopathogens in livestock.

Unraveling clonal CD8 T cell expansion and identification of essential factors in γ-herpesvirus-induced lymphomagenesis.

Alcelaphine gammaherpesvirus 1 (AlHV-1) asymptomatically persists in its natural host, the wildebeest. However, cross-species transmission to cattle results in the induction of an acute and lethal peripheral T cell lymphoma-like disease (PTCL), named malignant catarrhal fever (MCF). Our previous findings demonstrated an essential role for viral genome maintenance in infected CD8 T lymphocytes but the exact mechanism(s) leading to lymphoproliferation and MCF remained unknown.

Graduate Student Literature Review: The DRB3 gene of the bovine major histocompatibility complex-Discovery, diversity, and distribution of alleles in commercial breeds of cattle and applications for development of vaccines.

The bovine major histocompatibility complex (MHC), also known as the bovine leukocyte antigen (BoLA) complex, is the genomic region that encodes the most important molecules for antigen presentation to initiate immune responses. The first evidence of MHC in bovines pointed to a locus containing 2 antigens, one detected by cytotoxic antiserum (MHC class I) and another studied by mixed lymphocyte culture tests (MHC class II). The most studied gene in the BoLA region is the highly polymorphic BoLA-DRB3, which encodes a β chain with a peptide groove domain involved in antigen presentation for T cells that will develop and co-stimulate cellular and humoral effector responses.

MAIT cell-MR1 reactivity is highly conserved across multiple divergent species.

Mucosal-associated invariant T (MAIT) cells are a subset of unconventional T cells that recognize small molecule metabolites presented by major histocompatibility complex class I related protein 1 (MR1), via an αβ T cell receptor (TCR). MAIT TCRs feature an essentially invariant TCR α-chain, which is highly conserved between mammals. Similarly, MR1 is the most highly conserved major histocompatibility complex-I-like molecule.

Comparative transcriptional analysis identifies genes associated with the attenuation of Theileria parva infected cells after long-term in vitro culture.

Autologous administration of attenuated Theileria parva-infected cells induces immunity to T. parva in cattle. The mechanism of attenuation, however, is largely unknown.

Large scale transcriptional analysis of MHC class I haplotype diversity in sheep.

Domestic sheep (Ovis aries) have been an important component of livestock agricultural production for thousands of years. Preserving genetic diversity within livestock populations maintains a capacity to respond to changing environments and rapidly evolving pathogens. MHC genetic diversity can influence immune functionality at individual and population levels.

Development of lateral flow assays to detect host proteins in cattle for improved diagnosis of bovine tuberculosis.

Bovine tuberculosis (bTB), caused by () infection in cattle, is an economically devastating chronic disease for livestock worldwide. Efficient disease control measures rely on early and accurate diagnosis using the tuberculin skin test (TST) and interferon-gamma release assays (IGRAs), followed by culling of positive animals. Compromised performance of TST and IGRA, due to BCG vaccination or co-infections with non-tuberculous mycobacteria (NTM), urges improved diagnostics.

High-Resolution Genotyping of Expressed Equine MHC Reveals a Highly Complex MHC Structure.

The Major Histocompatibility Complex (MHC) genes play a key role in a number of biological processes, most notably in immunological responses. The MHCI and MHCII genes incorporate a complex set of highly polymorphic and polygenic series of genes, which, due to the technical limitations of previously available technologies, have only been partially characterized in non-model but economically important species such as the horse. The advent of high-throughput sequencing platforms has provided new opportunities to develop methods to generate high-resolution sequencing data on a large scale and apply them to the analysis of complex gene sets such as the MHC.

γδ TCRs Function as Innate-like Receptors in the Bovine γδ T Cell Response against Leptospira.

Leptospira serovar Hardjo are bacterial pathogens of cattle that also cause zoonotic disease in humans. Vaccine-mediated protection against Leptospira serovar Hardjo in cattle is associated with a workshop cluster 1 (WC1)+ γδ T cell response that can be recalled in vitro from PBMC by antigenic stimulation. This provides a model system in which to examine protective vaccine-induced γδ T cell responses in a γδ T cell high species.

Immunopeptidomic Analysis of BoLA-I and BoLA-DR Presented Peptides from Infected Cells.

The apicomplexan parasite Theileria parva is the causative agent of East Coast fever, usually a fatal disease for cattle, which is prevalent in large areas of eastern, central, and southern Africa. Protective immunity against T. parva is mediated by CD8+ T cells, with CD4+ T-cells thought to be important in facilitating the full maturation and development of the CD8+ T-cell response.

Protein Levels of Pro-Inflammatory Cytokines and Chemokines as Biomarkers of Infection and BCG Vaccination in Cattle.

Bovine tuberculosis (bTB), caused by , is a globally prevalent infectious disease with significant animal welfare and economic impact. Difficulties in implementing test-and-slaughter measures in low- and middle-income countries (LMICs) and the underperformance of the current diagnostics establish a clear need to develop improved diagnostics. Adaptive immunity biomarkers other than IFNγ could be useful as suggested by various gene expression studies; however, a comprehensive assessment at the protein level is lacking.

Next generation sequencing of transcribed genes in ruminant γδ T cell populations.

Bovine γδ T cells are distinguished by expression of WC1, hybrid pattern recognition receptors and co-receptors to the T cell receptor (TCR), or their absence. WC1 molecules bind pathogens and the ability of γδ T cells to respond to pathogens largely correlates with their expression of particular WC1 genes. Following activation, the TCR and WC1 molecules co-localize and knocking down WC1 abrogates the ability of WC1-expressing γδ T cells to respond to antigen.

Antibodies that react with bovine T lymphocytes expressing the T cell receptor β chain subgroup BV20 inhibit antigen recognition.

In recent years, molecular studies have provided detailed information on the bovine T cell receptor (TCR) variable gene repertoire, both in resting T cells and during T cell responses. However, studies of the biological function of the receptor have been hampered by a lack of reagents that recognise the protein. Herein, we describe the characterisation of two antibodies (IL-A47 and IL-A98) that recognise T cells expressing the TCR VB20 subfamily of BV genes.

Spatial, temporal and molecular dynamics of swine influenza virus-specific CD8 tissue resident memory T cells.

For the first time we have defined naïve, central memory, effector memory and differentiated effector porcine CD8 T cells and analyzed their distribution in lymphoid and respiratory tissues after influenza infection or immunization, using peptide-MHC tetramers of three influenza nucleoprotein (NP) epitopes. The hierarchy of response to the three epitopes changes during the response in different tissues. Most NP-specific CD8 T cells in broncho-alveolar lavage (BAL) and lung are tissue resident memory cells (TRM) that express CD69 and downregulate CD45RA and CCR7.

CD4 T Cell Responses to in Immune Cattle Recognize a Diverse Set of Parasite Antigens Presented on the Surface of Infected Lymphoblasts.

Parasite-specific CD8 T cell responses play a key role in mediating immunity against in cattle (), and there is evidence that efficient induction of these responses requires CD4 T cell responses. However, information on the antigenic specificity of the CD4 T cell response is lacking. The current study used a high-throughput system for Ag identification using CD4 T cells from immune animals to screen a library of ∼40,000 synthetic peptides representing 499 gene products.

Gamma Delta TCR and the WC1 Co-Receptor Interactions in Response to Using Imaging Flow Cytometry and STORM.

The WC1 cell surface family of molecules function as hybrid gamma delta (γδ) TCR co-receptors, augmenting cellular responses when cross-linked with the TCR, and as pattern recognition receptors, binding pathogens. It is known that following activation, key tyrosines are phosphorylated in the intracytoplasmic domains of WC1 molecules and that the cells fail to respond when WC1 is knocked down or, as shown here, when physically separated from the TCR. Based on these results we hypothesized that the colocalization of WC1 and TCR will occur following cellular activation thereby allowing signaling to ensue.

High throughput analysis of MHC-I and MHC-DR diversity of Brazilian cattle populations.

The major histocompatibility complex (MHC) contains many genes that play key roles in initiating and regulating immune responses. This includes the polymorphic MHCI and MHCII genes that present epitopes to CD8+ and CD4+ T-cells, respectively. Consequently, the characterisation of the repertoire of MHC genes is an important component of improving our understanding of the genetic variation that determines the outcomes of immune responses.

Identification and Phenotype of MAIT Cells in Cattle and Their Response to Bacterial Infections.

Mucosal-associated invariant T (MAIT) cells are a population of innate-like T cells that utilize a semi-invariant T cell receptor (TCR) α chain and are restricted by the highly conserved antigen presenting molecule MR1. MR1 presents microbial riboflavin biosynthesis derived metabolites produced by bacteria and fungi. Consistent with their ability to sense ligands derived from bacterial sources, MAIT cells have been associated with the immune response to a variety of bacterial infections, such as .

Characterization of the domestic goat γδ T cell receptor gene loci and gene usage.

Goats and cattle diverged 30 million years ago but retain similarities in immune system genes. Here, the caprine T cell receptor (TCR) gene loci and transcription of its genes were examined and compared to cattle. We annotated the TCR loci using an improved genome assembly (ARS1) of a highly homozygous San Clemente goat.

Hydrophobic Mycobacterial Antigens Elicit Polyfunctional T Cells in Immunized Cattle: Association With Protection Against Challenge?

Bovine tuberculosis (bTB), caused by , is a chronic disease of cattle with a detrimental impact on food quality and production. Research on bTB vaccines has predominantly been focused on proteinaceous antigens. However, mycobacteria have a thick and intricate lipid outer layer and lipids as well as lipopeptides are important for immune-evasion and virulence.