Lymphocyte Receptors Research Articles

An increase of the oncogenesis frequency is associated with the DAMPs accumulation and the killer cell subpopulations ratio change in patients with long-term post-COVID-19 syndrome

In patients with malignant lesions of the lungs and pancreas, the development of which was facilitated by the long-term post-COVID-19 syndrome (PCS), presence a significant increase (on average by 80%) in the serum content of the cytotoxic oligonucleotide fraction DAMP was found. High antigenic load due to the increase of DAMP contributed to the absorptive function growth and insufficient digestive function of neutrophils; decrease in the NADPH-catalase activity reserve in oxygen-dependent phagocytosis. An increase of CD16+ NK cells of innate immunity and an overexpression of CD8+ killer/suppressor T lymphocyte receptors of adaptive immunity in response to the suppressor coreceptors competitive action were revealed. These changes in cellular immunity were more pronounced in patients with malignant lung lesions and correlated with low serum conductivity. To predict the individual course of the disease, it is advisable to carry out screening measurements of electrical conductivity of blood serum and to determine the control points of innate and adaptive immunity changes in patients with comorbid pathology: PCS and an oncological process. In further studies, attention should be paid to the algorithm development of immunological and screening tests for the oncological diseases course prognosis and the treatment tactics effectiveness.

Passive immunoprophylaxis with Ccombodies against Vibrio parahaemolyticus in Pacific white shrimp (Penaeus vannamei)

The Vibrio parahaemolyticus strain causing acute hepatopancreatic necrosis disease (AHPND) in shrimp secretes toxins A and B (PirAVp/PirBVp). These toxins have been implicated in pathogenesis and are targets for developing anti-AHPND therapeutics or prophylactics that include passive immunization. We have previously reported that Ccombodies (recombinant hagfish variable lymphocyte receptor B antibodies; VLRB) targeting PirBVp conferred protection against V. parahaemolyticus in shrimp when administered as a feed supplement. In this study, we screened a phage-displayed library of engineered VLRBs for PirAVp-targeting Ccombodies that were mass-produced in a bacterial expression system. We then introduced these Ccombodies into the diet of Pacific white shrimp (Penaeus vannamei) over a seven-day period. Subsequently, the shrimp were exposed to a challenge with V. parahaemolyticus. Mortality rates were then observed and recorded over the following seven days. Administering shrimp feed supplemented with Ccombodies at a high dose (100 mg per 100 g feed) reduced mortality in recipient animals (2.96-5.19%) statistically similar to mock-challenged control (1.48%), but significantly different from the Ccombody-deficient control (74.81%). This suggests that the Ccombodies provided strong protection against the bacterium. Feeding shrimp with a median dose (10 mg/100 g feed) gave statistically comparable low mortality (5.93-6.67%) as the high dose. Reducing the Ccombody dose to 1 mg/100 g feed showed variable effects. Ccombody A2 showed mortality (11.85%) significantly lower than that of the Ccombody-deficient group (74.81%), suggesting that it can effectively protect against the bacterial challenge at a low dose. Our results demonstrate the ability of the phage-displayed VLRB library to generate antigen-specific Ccombodies rapidly and simply, with the expression of high protein levels in bacteria. The protective effect provided by these Ccombodies aligns with our earlier results, strongly supporting the use of VLRB antibodies as a substitute for IgY in passive immunoprophylaxis against AHPND in shrimp.

A lymphocyte chemoaffinity axis for lung, non-intestinal mucosae and CNS.

Tissue-selective chemoattractants direct lymphocytes to epithelial surfaces to establish local immune environments, regulate immune responses to food antigens and commensal organisms, and protect from pathogens. Homeostatic chemoattractants for small intestines, colon, and skin are known1 2, but chemotropic mechanisms selective for respiratory tract and other non-intestinal mucosal tissues (NIMT) remain poorly understood. Here we leveraged diverse omics datasets to identify GPR25 as a lymphocyte receptor for CXCL17, a chemoattractant cytokine whose expression by epithelial cells of airways, upper gastrointestinal and squamous mucosae unifies the NIMT and distinguishes them from intestinal mucosae. Single-cell transcriptomic analyses show that GPR25 is induced on innate lymphocytes prior to emigration to the periphery, and is imprinted in secondary lymphoid tissues on activated B and T cells responding to immune challenge. GPR25 characterizes B and T tissue resident memory and regulatory T lymphocytes in NIMT and lungs in humans and mediates lymphocyte homing to barrier epithelia of the airways, oral cavity, stomach, biliary and genitourinary tracts in mouse models. GPR25 is also expressed by T cells in cerebrospinal fluid and CXCL17 by neurons, suggesting a role in CNS immune regulation. We reveal widespread imprinting of GPR25 on regulatory T cells, suggesting a mechanistic link to population genetic evidence that GPR25 is protective in autoimmunity3,4. Our results define a GPR25-CXCL17 chemoaffinity axis with the potential to integrate immunity and tolerance at non-intestinal mucosae and the CNS.

Invariant VD and DJ Motifs Define a Novel Class of Human Antibodies and TCRs Prototyped by antigen receptors of Dual-Expresser Lymphocytes

ABSTRACT Introduction Dual-expressing lymphocytes (DEs) are unique immune cells that express both B cell receptors (BCRs, surface antibody) and T cell receptors (TCRs). In type 1 diabetes, DE antibodies are predominated by one antibody (x-mAb), an IgM monoclonal antibody with a germline-encoded CDR3 that recognizes self-reactive TCRs. We explored if x-mAb and its interacting TCRs have distinct structural features. Methods Using bioinformatics, we compared x-mAb and its most common interacting TCRαβ to billions of antigen receptor sequences to determine if they were unique or randomly generated. Results X-mAb represents a unique class of human antibodies with a conserved CDR3 sequence (CARx1-4DTAMVYYFYDW), consisting of a fixed DJH motif (DTAMVYYFDYW) paired with various VH genes. A public TCRβ clonotype (CASSPGTEAFF) associated with x-mAb on DEs features two invariant segments, VβD (CASSPGT) and DJβ (PGTEAFF), key to two large families of public TCRβ clonotypes—CASSPGT-Jβx and CASSPGT-Jβx—formed by recombining the VβD motif with Jβ genes and the DJβ motif with Vβ genes. B cells also use CASSPGT as a VHD motif for public IGH clonotypes (CASSPGT—Jβx). Discussion DEs, unlike conventional T and B cells, use invariant motifs to create public antibodies and TCRs, a trait previously seen only in cartilaginous fish.

Discovery of an unconventional lamprey lymphocyte lineage highlights divergent features in vertebrate adaptive immune system evolution

Lymphocyte receptors independently evolved in both jawed and jawless vertebrates with similar adaptive immune responses. However, the diversity of functional subtypes and molecular architecture in jawless vertebrate lymphocytes, comparable to jawed species, is not well defined. Here, we profile the gills, intestines, and blood of the lamprey, Lampetra morii, with single-cell RNA sequencing, using a full-length transcriptome as a reference. Our findings reveal higher tissue-specific heterogeneity among T-like cells in contrast to B-like cells. Notably, we identify a unique T-like cell subtype expressing a homolog of the nonlymphoid hematopoietic growth factor receptor, MPL-like (MPL-L). These MPL-L+ T-like cells exhibit features distinct from T cells of jawed vertebrates, particularly in their elevated expression of hematopoietic genes. We further discovered that MPL-L+ VLRA+ T-like cells are widely present in the typhlosole, gill, liver, kidney, and skin of lamprey and they proliferate in response to both a T cell mitogen and recombinant human thrombopoietin. These findings provide new insights into the adaptive immune response in jawless vertebrates, shedding new light on the evolution of adaptive immunity.

Surfactant system of the lungs in antiphospholipid syndrome under the conditions of administration of the immunosuppressive agent FTY-720

Antiphospholipid syndrome (APS) is a thrombophilic disease in the pathogenesis of which the leading role belongs to antibodies reacting with antigenic determinants of phospholipids. APS is a systemic autoimmune pathology that involves many organs and systems in the pathological process, including the respiratory system. Given the fact that the lung surfactant is mainly represented by phospholipids, it can be presented that the surfactant is damaged and its functioning is impaired in APS. The results of our experiments showed that in antiphospholipid syndrome, there was a decline in the functional activity of the surfactant and a change in its biochemical composition. The introduction of FTY-720 normalized the parameters of the lung surfactant system, which were changed during the modeling of antiphospholipid syndrome. The work shows the effectiveness of the therapy of this autoimmune pathology with immunosuppressor FTY-720, which is a structural analogue of endogenous sphingosine. The effect of the drug is based on the modulation of sphingosine-1 phosphate receptors of lymphocytes. The main effect of the immunosuppressor FTY-720 as a result of receptor interaction is a decrease in the number of circulating lymphocytes. The research involved 85 white random bred male rats: Group 1 (APS modeling) consisted of 30 rats who were intravenously injected with cardiolipin antigen at a total dose of 0.2-0.4 mg per rat every other day for three weeks; Group 2 (control) consisted of 25 rats who were injected with 0.9% NaCl solution according to the same scheme; and Group 3 including 30 rats in which APS was combined with the administration of the immunosuppressive agent FTY-720 (intraperitoneally 1 mg/kg of animal weight). Three weeks later, there was an operation conducted with the purpose of extraction of the bronchopulmonary complex. After extraction of the bronchopulmonary complex, its triple lavage was carried out with 0.9% NaCl solution. The material of the experimental study was a lavage liquid, in which the biophysical and biochemical parameters of the surfactant were studied. Langmuir–Blodgett method was used to identify static, minimal and maximal surface tension. These figures were used to identify integrative indicator reflecting surfactant characteristics – the Clements stability index. The fractional composition of surfactant phospholipids was determined by thin-layer chromatography. The results of our experiments showed that in antiphospholipid syndrome, there was a decline in the functional activity of the surfactant and a change in its biochemical composition. The introduction of FTY-720 normalized the parameters of the lung surfactant system, which were changed during the modeling of antiphospholipid syndrome.

High throughput long-read sequencing of circulating lymphocytes of the evolutionarily distant sea lamprey reveals diversity and common elements of the variable lymphocyte receptor B (VLRB) repertoire.

The leucine-rich repeat-based variable lymphocyte receptor B (VLRB) antibody system of jawless vertebrates is capable of generating an antibody repertoire equal to or exceeding the diversity of antibody repertoires of jawed vertebrates. Unlike immunoglobulin-based immune repertoires, the VLRB repertoire diversity is characterized by variable lengths of VLRB encoding transcripts, rendering conventional immunoreceptor repertoire sequencing approaches unsuitable for VLRB repertoire sequencing. Here we demonstrate that long-read single-molecule real-time (SMRT) sequencing (PacBio) approaches permit the efficient large-scale assessment of the VLRB repertoire. We present a computational pipeline for sequence data processing and provide the first repertoire-based analysis of VLRB protein characteristics including properties of its subunits and regions of diversity within each structural leucine-rich repeat subunit. Our study provides a template to explore changes in the VLRB repertoire during immune responses and to establish large scale VLRB repertoire databases for computational approaches aimed at isolating monoclonal VLRB reagents for biomedical research and clinical applications.

The identification of effective tumor-suppressing neoantigens using a tumor-reactive TIL TCR-pMHC ternary complex

Neoantigens are ideal targets for cancer immunotherapy because they are expressed de novo in tumor tissue but not in healthy tissue and are therefore recognized as foreign by the immune system. Advances in next-generation sequencing and bioinformatics technologies have enabled the quick identification and prediction of tumor-specific neoantigens; however, only a small fraction of predicted neoantigens are immunogenic. To improve the predictability of immunogenic neoantigens, we developed the in silico neoantigen prediction workflows VACINUSpMHC and VACINUSTCR: VACINUSpMHC incorporates physical binding between peptides and MHCs (pMHCs), and VACINUSTCR integrates T cell reactivity to the pMHC complex through deep learning-based pairing with T cell receptors (TCRs) of putative tumor-reactive CD8 tumor-infiltrating lymphocytes (TILs). We then validated our neoantigen prediction workflows both in vitro and in vivo in patients with hepatocellular carcinoma (HCC) and in a B16F10 mouse melanoma model. The predictive abilities of VACINUSpMHC and VACINUSTCR were confirmed in a validation cohort of 8 patients with HCC. Of a total of 118 neoantigen candidates predicted by VACINUSpMHC, 48 peptides were ultimately selected using VACINUSTCR. In vitro validation revealed that among the 48 predicted neoantigen candidates, 13 peptides were immunogenic. Assessment of the antitumor efficacy of the candidate neoepitopes using a VACINUSTCR in vivo mouse model suggested that vaccination with the predicted neoepitopes induced neoantigen-specific T cell responses and enabled the trafficking of neoantigen-specific CD8 + T cell clones into the tumor tissue, leading to tumor suppression. This study showed that the prediction of immunogenic neoantigens can be improved by integrating a tumor-reactive TIL TCR-pMHC ternary complex.

Design of targeted antiviral polypeptides specific to SARS-CoV-2. Challenges and prospects

The COVID-19 epidemic demanded the rapid development of high-affinity molecules of different types aimed at a single target, the S-protein of SARS-CoV-2. The simultaneous development and testing of such molecules provide a unique opportunity to compare the features of biotechnological platforms for creating therapeutic proteins. This review considers classical antibodies, variable lymphocyte receptors, single-domain antibodies, and artificial scaffolds (DARPins, affibodies, VH), that are compared in terms of affinity, neutralizing activity, size and compatibility with different delivery methods. It can be concluded that all platforms used have produced high-affinity proteins that specifically bind to the coronavirus S-protein. The highest affinity of the targeting molecules with the virus protein was achieved by developing classical antibodies, nanobodies and by combining several binding modules into multivalent constructs with high avidity. Based on the results of <i>in vivo</i> experiments, it can be concluded that a high affinity of the therapeutic protein for the surface antigens of SARS-CoV-2 is a necessary but not sufficient condition for suppression of COVID-19 due to the peculiarities of the biology of this virus. The experience gained in the development of therapeutic agents against coronavirus will be useful for design of effective targeted drugs for the treatment of known and new viral infections.<br>The bibliography includes 126 references.

MRNA Expression of Dopamine Receptors in Peripheral Blood Lymphocytes of Social Networking Sites (SNS) Addicts: A Case-Control Study

Background: The increasing importance of and reliance on social networking sites (SNS) has led people to frequent usage and addiction. The dopaminergic system plays a crucial role in the addiction process. Additionally, research suggests that the level of expression of brain neurotransmitter receptors may be reflected in peripheral blood lymphocytes. Objectives: This study aimed to investigate the expression of dopamine receptors in peripheral blood lymphocytes (PBL) among SNS addicts and their relatives. Patients and Methods: The mRNA expression of dopamine D3, D4, and D5 receptors in peripheral blood lymphocytes was assessed using real-time PCR in SNS addicts (n = 10) and their first-degree relatives (n = 10) compared with normal subjects (n = 10). Results: The findings revealed a significant decrease in D5 and D4 receptor mRNA expression in the PBL of SNS addicts compared to the control group (P < 0.05). In contrast, D3 receptor mRNA levels showed no significant change (P > 0.05). First-degree relatives of SNS addicts also exhibited a significant decrease in D5 receptor mRNA levels compared to the control group (P < 0.05), but unlike SNS addicts, D4 receptor levels did not show any significant decrease. D3 levels also remained unchanged (P > 0.05). Conclusions: Based on the results of this study, considering the genetic factors that strongly influence social network addiction, necessary measures should be implemented to prevent this type of addiction in families and institutions such as schools and universities.

JAK/STAT3 represents a therapeutic target for colorectal cancer patients with stromal-rich tumors

Colorectal cancer (CRC) is a heterogenous malignancy underpinned by dysregulation of cellular signaling pathways. Previous literature has implicated aberrant JAK/STAT3 signal transduction in the development and progression of solid tumors. In this study we investigate the effectiveness of inhibiting JAK/STAT3 in diverse CRC models, establish in which contexts high pathway expression is prognostic and perform in depth analysis underlying phenotypes. In this study we investigated the use of JAK inhibitors for anti-cancer activity in CRC cell lines, mouse model organoids and patient-derived organoids. Immunohistochemical staining of the TransSCOT clinical trial cohort, and 2 independent large retrospective CRC patient cohorts was performed to assess the prognostic value of JAK/STAT3 expression. We performed mutational profiling, bulk RNASeq and NanoString GeoMx® spatial transcriptomics to unravel the underlying biology of aberrant signaling. Inhibition of signal transduction with JAK1/2 but not JAK2/3 inhibitors reduced cell viability in CRC cell lines, mouse, and patient derived organoids (PDOs). In PDOs, reduced Ki67 expression was observed post-treatment. A highly significant association between high JAK/STAT3 expression within tumor cells and reduced cancer-specific survival in patients with high stromal invasion (TSPhigh) was identified across 3 independent CRC patient cohorts, including the TrasnSCOT clinical trial cohort. Patients with high phosphorylated STAT3 (pSTAT3) within the TSPhigh group had higher influx of CD66b + cells and higher tumoral expression of PDL1. Bulk RNAseq of full section tumors showed enrichment of NFκB signaling and hypoxia in these cases. Spatial deconvolution through GeoMx® demonstrated higher expression of checkpoint and hypoxia-associated genes in the tumor (pan-cytokeratin positive) regions, and reduced lymphocyte receptor signaling in the TME (pan-cytokeratin- and αSMA-) and αSMA (pan-cytokeratin- and αSMA +) areas. Non-classical fibroblast signatures were detected across αSMA + regions in cases with high pSTAT3. Therefore, in this study we have shown that inhibition of JAK/STAT3 represents a promising therapeutic strategy for patients with stromal-rich CRC tumors. High expression of JAK/STAT3 proteins within both tumor and stromal cells predicts poor outcomes in CRC, and aberrant signaling is associated with distinct spatially-dependant differential gene expression.

Study of vitamin D levels in patients with allergic rhinitis

Allergic rhinitis (AR) is the most common type of chronic rhinitis, affecting 10-20% of the population. Severe allergic rhinitis has been associated with significant impairments in quality of life, sleep, and work performance. Vitamin D and its role in regulation of immune function was first proposed after the identification of vitamin D receptors in lymphocytes. There are recent researches linking vitamin D to various immune-related conditions, including allergy, although the pattern of this relationship is still yet to establish. Methods and materials: an observational descriptive study conducted in the Outpatient Department of ENT of Sri Siddhartha Medical College, Tumkur, Karnataka, over a period of 1 year comprising of around 40 patients from 18-65 years of age suffering from allergic rhinitis patients were scored using Total nasal symptoms scoring system (TNSS) based on nasal symptoms. Also, Vitamin D levels are measured and based on these levels patients are graded. Results: Among 40 patients, male predominance with 23(57.5%) cases with mean age of 38.4 +/- 6.8. Majority of patients were in 7-10 TNSS with 15 patients accounting for 37.5%. Patients with severe allergic symptoms had mean vitamin D level about 19.6 +/- 4.2 ng/dl, patients with moderate symptoms were seen with mean vitamin D level 28.6 +/- 3.6 ng/dl and with mild symptoms 34.4+/- 2.8 ng/dl and the p value was significant (<0.04) in our study. Conclusion: Vitamin D could improve allergy symptoms directly or indirectly by potentiating the anti-inflammatory effects of the medications used to treat allergy.

Signaling lymphocytic activation molecule family receptors as potential immune therapeutic targets in solid tumors.

Recently, cancer immunotherapy has revolutionized cancer treatment. Various forms of immunotherapy have a manageable safety profile and result in prolongation of overall survival in patients with solid tumors, but only in a proportion of patients. Various factors in the tumor microenvironment play critical roles and may be responsible for this lack of therapeutic response. Signaling lymphocytic activation molecule family (SLAMF) members are increasingly being studied as factors impacting the tumor immune microenvironment. SLAMF members consist of nine receptors mainly expressed in immune cells. However, SLAMF receptors have also been detected in cancer cells, and they may be involved in a spectrum of anti-tumor immune responses. Here, we review the current knowledge of the expression of SLAMF receptors in solid tumors and tumor-infiltrating immune cells and their association with patient outcomes. Furthermore, we discuss the therapeutic potential of targeting SLAMF receptors to improve outcomes of cancer therapy in solid tumors. We believe the research on SLAMF receptor-targeted strategies may enhance anti-cancer immunity in patients with solid tumors and improve clinical outcomes.

Soluble CD27 as a predictive biomarker for intra-tumoral CD70/CD27 interaction in nasopharyngeal carcinoma.

In CD70-expressing tumors, the interaction of CD70 on tumor cells with its lymphocyte receptor, CD27, is thought to play a role in immunosuppression in the tumor microenvironment and elevated serum levels of soluble CD27 (sCD27). Previous studies showed that CD70 is expressed in nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-related malignancy. However, the association between intratumoral CD70/CD27 expression and serum levels of sCD27 in NPC remains unclear. In the present study, we show that CD70 is primarily expressed by tumor cells in NPC and that CD27-positive lymphocytes infiltrate around tumor cells. NPC patients with CD27-positive lymphocytes had significantly better prognosis than patients lacking these cells. In addition, high CD70 expression by tumor cells tended to be correlated with shorter survival in NPC patients with CD27-positive lymphocytes. Serum sCD27 levels were significantly increased in patients with NPC and provided good diagnostic accuracy for discriminating patients from healthy individuals. The concentration of serum sCD27 in patients with CD70-positive NPC with CD27-positive lymphocytes was significantly higher than in patients with tumors negative for CD70 and/or CD27, indicating that the intratumoral CD70/CD27 interaction boosts the release of sCD27. Furthermore, positive expression of CD70 by NPC cells was significantly correlated with EBV infection. Our results suggest that CD70/CD27-targeted immunotherapies may be promising treatment options and that sCD27 may become an essential tool for evaluating the applicability of these therapies by predicting the intratumoral CD70/CD27 interaction in NPC.

Host glycosylation of immunoglobulins impairs the immune response to acute Lyme disease

Lyme disease is caused by the bacteria Borreliella burgdorferi sensu lato (Bb) transmitted to humans from the bite of an infected Ixodes tick. Current diagnostics for Lyme disease are insensitive at the early disease stage and they cannot differentiate between active infections and people with a recent history of antibiotic-treated Lyme disease. Machine learning technology was utilized to improve the prediction of acute Lyme disease and identify sialic acid and galactose sugar structures (N-glycans) on immunoglobulins associated specifically at time points during acute Lyme disease time. A plate-based approach was developed to analyze sialylated N-glycans associated with anti-Bb immunoglobulins. This multiplexed approach quantitates the abundance of Bb-specific IgG and the associated sialic acid, yielding an accuracy of 90% in a powered study. It was demonstrated that immunoglobulin sialic acid levels increase during acute Lyme disease and following antibiotic therapy and a 3-month convalescence, the sialic acid level returned to that found in healthy control subjects (p<0.001). Furthermore, the abundance of sialic acid on Bb-specific IgG during acute Lyme disease impaired the host's ability to combat Lyme disease via lymphocytic receptor FcγRIIIa signaling. After enzymatically removing the sialic acid present on Bb-specific antibodies, the induction of cytotoxicity from acute Lyme disease patient antigen-specific IgG was significantly improved. Taken together, Bb-specific immunoglobulins contain increased sialylation which impairs the host immune response during acute Lyme disease. Furthermore, this Bb-specific immunoglobulin sialyation found in acute Lyme disease begins to resolve following antibiotic therapy and convalescence. Funding for this study was provided by the Coulter-Drexel Translational Research Partnership Program as well as from a Faculty Development Award from the Drexel University College of Medicine Institute for Molecular Medicine and Infectious Disease and the Department of Microbiology and Immunology.

A Hybrid Design for the Functional Assay of LvLRRm (Protein Containing LRR Domain) of the White Leg Shrimp, Litopenaeus vannamei

In the crustacean immune system, leucine-rich repeat (LRR) is one of the major structures for recognizing pathogen-associated molecular patterns (PAMPs). LRR domain-containing proteins belong to the LRR family, which is a large group of proteins with more than 6000 genes in the database. They are involved in very diverse physiological functions, mainly by interacting with other proteins. In a previous study, the LvLRRm, a transmembrane protein containing only LRR domain, was identified in the white leg shrimp, Litopenaeus vannamei. Its versatile role in performing multiple immunomodulation activities has been reported. However, there is still a lack of research on its efficient function at the protein level. To investigate its interactions with other proteins, we applied a convenient method called the ‘Hybrid LRR technique’ to produce a recombinant LvLRRm. The LvLRRm and hagfish’s variable lymphocyte receptors (VLRs) fragments were fused to the conserved LxxLxLxxN motif while retaining the β-strand. In addition, we established interactions between hybrid proteins and the flagellin of Salmonella typhimurium by performing surface plasmon resonance (SPR) analysis. The results of the SPR analysis demonstrated notable affinity for both LvLRRm and hybrid proteins towards Salmonella flagellin. The designed LvLRRm hybrid proteins bring insight for universal applications without losing protein functions.

Erratum for Velasco-de Andrés et al., "The Lymphocytic Scavenger Receptor CD5 Shows Therapeutic Potential in Mouse Models of Fungal Infection".

Erratum for Velasco-de Andrés et al., "The Lymphocytic Scavenger Receptor CD5 Shows Therapeutic Potential in Mouse Models of Fungal Infection".

Pattern recognition receptors involved in the immune system of hagfish (Eptatretus burgeri)

The initial defense against invading pathogenic microbes is the activation of innate immunity by binding of pattern recognition receptors (PRRs) to pathogen associated molecular patterns (PAMPs). To explain the action of PRRs from hagfish, one of the extant jawless vertebrates, we purified the GlcNAc recognition complex (GRC) from serum using GlcNAc-agarose. The GRC comprises four proteins of varying molecular masses: 19 kDa, 26 kDa, 27 kDa, and 31 kDa. Exposure of Escherichia coli to the GRC led to the phagocytic activation of macrophages, revealing the opsonic function of the GRC. The GRC in serum formed a large complex with a molecular mass of approximately 1200 kDa. The GRC bound to Escherichia coli but not to rabbit red blood cells, despite both having GlcNAc on their surface. These structural and binding properties are similar to those of mannose-binding lectin (MBL). The amino acid sequence of a portion of the 31 kDa protein in the GRC matched the amino acid sequence of variable lymphocyte receptor (VLR)-B in some place. According to the Western blot analysis, the 31 kDa protein was recognized by the anti-hagfish VLR-B antiserum. Based on the results, it appears that the GRC functions as a PRR like MBL and that its 31 kDa protein has a structure similar to that of VLR-B.

Acquired Immune Deficiency Syndrome correlation with SARS-CoV-2 N genotypes

BackgroundEpigenetics and clinical observations referring to Betacoronavirus lead to the conjecture that Sarbecovirus may have the ability to infect lymphocytes using a different way than the spike protein. In addition to inducing the death of lymphocytes, thus drastically reducing their population and causing a serious immune deficiency, allows it to remain hidden for long periods of latency using them as a viral reservoir in what is named Long-Covid Disease. Exploring possibilities, the hypothesis is focused on that N protein may be the key of infecting lymphocytes. MethodThe present article exhibits a computational assay for the latest complete sequences reported to GISAID, correlating N genotypes with an enhancement in the affinity of the complex that causes immune deficiency in order to determine a good docking with the N protein and some receptors in lymphocytes. ResultsA novel high-interaction coupling of N-RBD and CD147 is presented as the main way of infecting lymphocytes, allowing to define those genotypes involved in their affinity enhancement. ConclusionThe hypothesis is consistent with the mutagenic deriving observed on the in-silico assay, which reveals that genotypes N/120 and N/152 are determinant to reduce the Immune Response of the host infecting lymphocytes, allowing the virus persists indefinitely and causing an Acquire Immune Deficiency Syndrome.

Decision trees to evaluate the risk of developing multiple sclerosis.

Multiple sclerosis (MS) is a persistent neurological condition impacting the central nervous system (CNS). The precise cause of multiple sclerosis is still uncertain; however, it is thought to arise from a blend of genetic and environmental factors. MS diagnosis includes assessing medical history, conducting neurological exams, performing magnetic resonance imaging (MRI) scans, and analyzing cerebrospinal fluid. While there is currently no cure for MS, numerous treatments exist to address symptoms, decelerate disease progression, and enhance the quality of life for individuals with MS. This paper introduces a novel machine learning (ML) algorithm utilizing decision trees to address a key objective: creating a predictive tool for assessing the likelihood of MS development. It achieves this by combining prevalent demographic risk factors, specifically gender, with crucial immunogenetic risk markers, such as the alleles responsible for human leukocyte antigen (HLA) class I molecules and the killer immunoglobulin-like receptors (KIR) genes responsible for natural killer lymphocyte receptors. The study included 619 healthy controls and 299 patients affected by MS, all of whom originated from Sardinia. The gender feature has been disregarded due to its substantial bias in influencing the classification outcomes. By solely considering immunogenetic risk markers, the algorithm demonstrates an ability to accurately identify 73.24% of MS patients and 66.07% of individuals without the disease. Given its notable performance, this system has the potential to support clinicians in monitoring the relatives of MS patients and identifying individuals who are at an increased risk of developing the disease.