English
French
Molecular immunology.
Publisher:
Pergamon Press.
Frequency: Eighteen no. a year
Country: England
Language: English
Start Year:1979 -
ISSN:
0161-5890 (Print)
1872-9142 (Electronic)
0161-5890 (Linking)
1872-9142 (Electronic)
0161-5890 (Linking)
Impact Factor
3.6
2022
| NLM ID: | 7905289 |
| (DNLM): | M43350000(s) |
| (OCoLC): | 03979267 |
| Coden: | MOIMD5 |
| Classification: | W1 MO196K |
The impact of Escherichia coli contamination products present in recombinant African horse sickness virus serotype 4 proteins on the innate and humoral immune responses. Transcriptome analysis was used to characterise the in vitro primary and secondary immune responses induced in horse peripheral blood mononuclear cells (PBMC) stimulated for 24 h with the individual recombinant proteins of a virulent AHSV serotype 4 (AHSV4) field isolate (rAHSV4 proteins) that were previously expressed in Escherichia coli (E. coli). The results showed that the E. coli contamination products greatly affected the innate and humoral immune response transcripts. Hence, the impact of E. coli contamination products present in the individual rAHSV4 proteins on the translational immu...
The major role of junctional diversity in the horse antibody repertoire. The antibody repertoire (Rep-seq) sequencing revolutionized the diversity of antigen B cell receptor studies, allowing deep and quantitative analysis to decipher the role of adaptive immunity in health and disease. Particularly, horse (Equus caballus) polyclonal antibodies have been produced and used since the century XIX to treat and prophylaxis diphtheria, tuberculosis, tetanus, pneumonia, and, more recently, COVID-19. However, our knowledge about the horse B cell receptors repertories is minimal. We present a deep horse antibody heavy chain repertoire (IGH) characterization of non-infected ...
Viral infection and allergy – What equine immune responses can tell us about disease severity and protection. Horses have many naturally occurring diseases that mimic similar conditions in humans. The ability to conduct environmentally controlled experiments and induced disease studies in a genetically diverse host makes the horse a valuable intermediate model between mouse studies and human clinical trials. This review highlights important similarities in the immune landscape between horses and humans using current research on two equine diseases as examples. First, equine herpesvirus type 1 (EHV-1) infection initiates a series of innate inflammatory signals at its mucosal entry site in the upper res...
Next-generation sequencing reveals new insights about gene usage and CDR-H3 composition in the horse antibody repertoire. Horse serum antibodies have been used for greater than a century for the treatment and prophylaxis of infectious diseases and envenomations. Little is known, however, about the immunogenetic diversity that produces horse serum antibodies. Here, we employed next-generation sequencing for a first-in-kind comprehensive analysis of the equine B-cell repertoire. Nearly 45,000 and 30,000 clonotypes were obtained for the heavy-chain (IGH) and lambda light-chain (IGL) loci, respectively. We observed skewed use of the common subgroups IGHV2 (92.49%) and IGLV8 (82.50%), consistent with previous reports,...
Sequence and functional variability of Toll-like receptor 9 gene in equines. Significant structural differences in the extracellular domain of toll-like receptor 9 (TLR9) account for species-specific recognition of its ligand CpG-ODN sequences. TLR9 is extensively studied in human, mice and some domestic animals. The recognition ability appears to be utilized differently by various species and breeds, but so far no comprehensive study exists about the equine TLR9 gene. We characterized TLR9 sequences of Marwari and Zanskari breeds of horses and Poitu donkey. We sequenced and identified the protein coding regions of equine TLR9 and compared with other animals and human ...
Crystal structure of equine serum albumin in complex with cetirizine reveals a novel drug binding site. Serum albumin (SA) is the main transporter of drugs in mammalian blood plasma. Here, we report the first crystal structure of equine serum albumin (ESA) in complex with antihistamine drug cetirizine at a resolution of 2.1Å. Cetirizine is bound in two sites--a novel drug binding site (CBS1) and the fatty acid binding site 6 (CBS2). Both sites differ from those that have been proposed in multiple reports based on equilibrium dialysis and fluorescence studies for mammalian albumins as cetirizine binding sites. We show that the residues forming the binding pockets in ESA are highly conserved in h...
Asthma “of horses and men”–how can equine heaves help us better understand human asthma immunopathology and its functional consequences? Animal models have been studied to unravel etiological, immunopathological, and genetic attributes leading to asthma. However, while experiments in which the disease is artificially induced have helped discovering biological and molecular pathways leading to allergic airway inflammation, their contribution to the understanding of the causality of the disease has been more limited. Horses naturally suffer from an asthma-like condition called "heaves" which presents sticking similarities with human asthma. It is characterized by reversible airway obstruction, airway neutrophilic inflammation, an...
The equine immune responses to infectious and allergic disease: a model for humans? The modern horse, Equus caballus has historically made important contributions to the field of immunology, dating back to Emil von Behring's description of curative antibodies in equine serum over a century ago. While the horse continues to play an important role in human serotherapy, the mouse has replaced the horse as the predominant experimental animal in immunology research. Nevertheless, continuing efforts have led to an improved understanding of the equine immune response in a variety of infectious and non-infectious diseases. Based on this information, we can begin to identify specific ...
Structural and antigenic features of the synthetic SF23 peptide corresponding to the receptor binding fragment of diphtheria toxin. The SF23 peptide corresponding to the receptor binding fragment of diphtheria toxin (residues 508-530) has been synthesized. This fragment forming a protruding beta hairpin has been chosen because it is the less mutable B-cell epitope. Affine chromatography and ELISA show that antibodies from the sera of persons infected by toxigenic Corynebacterium diphtheriae and those immunized by diphtheria toxoid are able to bind the synthetic SF23 peptide. There are antibodies recognizing the SF23 peptide in the serum of horses hyperimmunized with diphtheria toxoid. Analysis of circular dichroism spectra...
Engineering of a recombinant trivalent single-chain variable fragment antibody directed against rabies virus glycoprotein G with improved neutralizing potency. Human and equine rabies immunoglobulins are currently available for passive immunization against rabies. However, these are hampered by the limited supply and some drawbacks. Advances in antibody engineering have led to overcome issues of clinical applications and to improve the protective efficacy. In the present study, we report the generation of a trivalent single-chain Fv (scFv50AD1-Fd), that recognizes the rabies virus glycoprotein, genetically fused to the trimerization domain of the bacteriophage T4 fibritin, termed 'foldon' (Fd). scFv50AD1-Fd was expressed as soluble recombinant protei...
Structural and immunologic characterization of bovine, horse, and rabbit serum albumins. Serum albumin (SA) is the most abundant plasma protein in mammals. SA is a multifunctional protein with extraordinary ligand binding capacity, making it a transporter molecule for a diverse range of metabolites, drugs, nutrients, metals and other molecules. Due to its ligand binding properties, albumins have wide clinical, pharmaceutical, and biochemical applications. Albumins are also allergenic, and exhibit a high degree of cross-reactivity due to significant sequence and structure similarity of SAs from different organisms. Here we present crystal structures of albumins from cattle (BSA), h...
Expression of essential B cell development genes in horses with common variable immunodeficiency. Common variable immunodeficiency (CVID) is a heterogeneous disorder of B cell differentiation or function with inadequate antibody production. Our laboratory studies a natural form of CVID in horses characterized by late-onset B cell lymphopenia due to impaired B cell production in the bone marrow. This study was undertaken to assess the status of B cell differentiation in the bone marrow of CVID-affected horses by measuring the expression of genes essential for early B cell commitment and development. Standard RT-PCR revealed that most of the transcription factors and key signaling molecules ...
Kassorins: novel innate immune system peptides from skin secretions of the African hyperoliid frogs, Kassina maculata and Kassina senegalensis. From defensive skin secretions acquired from two species of African hyperoliid frogs, Kassina maculata and Kassina senegalensis, we have isolated two structurally related, C-terminally amidated tridecapeptides of novel primary structure that exhibit a broad spectrum of biological activity. In reflection of their structural novelty and species of origin, we named the peptides kassorin M (FLEGLLNTVTGLLamide; 1387.8 Da) and kassorin S (FLGGILNTITGLLamide; 1329.8 Da), respectively. The primary structure and organisation of the biosynthetic precursors of kassorins M and S were deduced from cloned s...
The different effector function capabilities of the seven equine IgG subclasses have implications for vaccine strategies. Recombinant versions of the seven equine IgG subclasses were expressed in CHO cells. All assembled into intact immunoglobulins stabilised by disulphide bridges, although, reminiscent of human IgG4, a small proportion of equine IgG4 and IgG7 were held together by non-covalent bonds alone. All seven IgGs were N-glycosylated. In addition IgG3 appeared to be O-glycosylated and could bind the lectin jacalin. Staphylococcal protein A displayed weak binding for the equine IgGs in the order: IgG1>IgG3>IgG4>IgG7>IgG2=IgG5>IgG6. Streptococcal protein G bound strongly to IgG1, IgG4 and IgG7, moderately t...
Major retinal autoantigens remain stably expressed during all stages of spontaneous uveitis. Equine recurrent uveitis (ERU) is a valuable model for autoimmune diseases, since it develops frequently and occurs spontaneously. We investigated the overall expression level of three major retinal autoantigens in normal retinas and various ERU stages. Analysis of retinal proteomes of both, healthy and diseased retinas revealed an almost unaffected expression of IRBP, S-antigen and cRALBP in ERU cases. Validation of these findings with western blots and immunohistochemistry confirmed constant to increased expression of these autoantigens, although loss of their physiological expression sites ...
Analysis of the horse V(H) repertoire and comparison with the human IGHV germline genes, and sheep, cattle and pig V(H) sequences. We have constructed a chimeric antibody single-chain Fv (scFv) fragments phage-displayed library that combines an invariant human V(L) chain with the repertoire of V(H) domains amplified from a horse immunized against scorpion venom. To gain insight into the equine V(H) repertoire, the V(H) sequences of 46 unique clones randomly chosen from the library prior to antigenic selection were analyzed. Comparisons with previously reported equine V(H) sequences, as well as with the repertoire of human IGHV germline genes and known V(H) sequences of sheep, cattle and pig, suggest that the equine IGH lo...
Horse complement protein C9: primary structure and cytotoxic activity. Lack of hemolytic activity of horse serum is an inherent property of horse C9. To understand the molecular reasons for this deficiency we have cloned C9 cDNA from a horse liver cDNA library and have sequenced the cDNA yielding the complete coding sequence for horse C9. Purification of C9 from horse plasma and microsequencing established the N-terminus of the mature protein and verified that the correct horse C9 cDNA clone had been isolated. The deduced amino acid sequence corresponds to a mature protein of 526 amino acids that is 77% identical to human C9. It has the same domain structure as h...
The complete cDNA and deduced amino acid sequence of equine IgE. The cDNA from a transcript encoding the complete heavy chain of the equine immunoglobulin IgE has been cloned and sequenced. A fragment of the equine epsilon gene was amplified from cDNA using PCR and this fragment was then used to probe a horse cDNA library prepared from peripheral blood lymphocytes. A recombinant clone containing the cDNA encoding the complete horse epsilon chain and its associated V-D-J and leader, was subsequently isolated and sequenced. Comparison of the deduced amino acid sequence of equine IgE with the C epsilon heavy chains of other species indicates it to be most simi...
Isolation and partial characterization of bovine and equine factor D. Bovine and equine factor D were purified to apparent homogeneity as evidenced by a single protein staining band on 7.5-17.5% SDS-PAGE slab gels under both reducing and non-reducing conditions. An apparent mol. wt of 15,000 for bovine D and 22,500 for equine D were noted after SDS-PAGE gel analysis of both reduced and non-reduced preparations. A single polypeptide chain for both proteins was evidenced by the lack of any change in the electrophoretic mobility under each of these conditions. The bovine and equine D were enriched 3347- and 9447-fold, with a 20 and 29% yield of hemolytic activity, ...
Immunochemical studies of infectious mononucleosis–XI. comparison of heterophile antibody inhibitors from the erythrocyte membranes of four mammalian species. Immunochemical comparisons were made of the reactivity of membrane glycoproteins from horse, bovine, sheep and goat erythrocytes with heterophile antibodies of infectious mononucleosis. The four receptors were tested as competitive inhibitors of a sandwich-type solid-phase radioimmunoassay and of agglutination of glycoprotein-latex reagents by infectious mononucleosis serum. The results of this study showed that the bovine glycoprotein had a superior reactivity with this heterophile antibody system and sheep erythrocyte glycoprotein was the least reactive. The latter had negligible ability to ...
