Complex Antigens Research Articles

Targeted Therapies: The Role of Monoclonal Antibodies in Disease Management.

Monoclonal antibodies (mAbs) are a key class of biotherapeutic medicines used to treat a wide range of diseases, such as cancer, infectious diseases, autoimmune disorders, cardiovascular diseases, and hemophilia. They can be engineered for greater effectiveness and specific applications while maintaining their structural elements for immune targeting. Traditional immunoglobulin treatments have limited therapeutic uses and various adverse effects. That makes mAbs show rapid growth in the pharmaceutical market, with over 250 mAbs in clinical studies. Although mAbs offer higher specificity, they are less effective against complex antigens. They have become essential in treating diseases with limited medical options, providing innovative solutions that improve patients' quality of life through increasing survival rates, shortening the length of stay in hospitals with an improved treatment outcome, and reducing side effects. This review outlines the mechanisms, applications, and advancements of mAbs, highlighting their transformative role in modern medicine and their potential to shape future therapeutic interventions.

Characterization of Urine-Derived Stromal/Stem Cells from Healthy Dogs and Dogs Affected by Chronic Kidney Disease (CKD).

Urine-derived mesenchymal stromal/stem cells (USCs) could be a valuable source of cells in regenerative medicine because urine can be easily collected non-invasively. In this paper, USCs were isolated from both healthy dogs and dogs affected by chronic kidney disease (CKD), and the efficacy of collection methods (spontaneous micturition, bladder catheterization, and cystocentesis) were compared. Isolated cells were cultured in the presence of platelet-rich plasma and studied for their proliferative capacity (growth curve, doubling time, and colony forming unit), differentiation properties, expression of mesenchymal markers, and Klotho protein. Morphologically, all cells were elongated and fibroblast-like. USCs isolated from samples collected by spontaneous micturition and bladder catheterization failed to proliferate, whilst USCs obtained by cystocentesis showed a doubling time of 2.04 days in healthy dogs and 1.7 days in dogs with CKD (p < 0.05). Cells were able to differentiate into osteogenic, chondrogenic, and adipogenic lines, showed positive expression to mesenchymal/stem markers, negative expression to hematopoietic markers, and major histocompatibility complex (MHCII) antigen. Klotho protein expression was confirmed. This study confirmed that USCs from healthy and CKD dogs can act as stem cells, with those from sick dogs having greater proliferative ability with the potential for use as autologous therapies.

Single-cell RNA-seq reveals immune cell heterogeneity and increased Th17 cells in human fibrotic skin diseases.

Fibrotic skin disease represents a major global healthcare burden, characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix components. The immune cells are postulated to exert a pivotal role in the development of fibrotic skin disease. Single-cell RNA sequencing has been used to explore the composition and functionality of immune cells present in fibrotic skin diseases. However, these studies detected the gene expression of all cells in fibrotic skin diseases and did not enrich immune cells. Thus, the precise immune cell atlas in fibrotic skin diseases remains unknown. In this study, we plan to investigate the intricate cellular landscape of immune cells in keloid, a paradigm of fibrotic skin diseases. CD45+ immune cells were enriched by fluorescence-activated cell sorting. Single-cell RNA sequencing was used to analyze the cellular landscape of immune cells in keloid and normal scar tissues. Ki-67 staining, a scratch experiment, real-time PCR, and Western blotting were used to explore the effect of the Th17 cell supernatant on keloid fibroblasts. Our findings revealed the intricate cellular landscape of immune cells in fibrotic skin diseases. We found that the percentage of Th17 cells was significantly increased in keloids compared to normal scars. All the subclusters of macrophages and dendritic cells (DCs) showed similar proportions between keloid samples and normal scar samples. However, upregulated genes in keloid M1 macrophages, M2 macrophages, and cDC2 are associated with the MHC class II protein complex assembly and antigen assembly, indicating that macrophages and cDC2 are active in keloids. Functional studies suggested that the supernatant of Th17 cells could promote proliferation, collagen expression, and migration of keloid fibroblasts through interleukin 17A. Importantly, increased Th17 cells are also found in other fibrotic skin diseases, such as hypertrophic scars and scleroderma, suggesting this represents a broad mechanism for skin fibrosis. In summary, we built a single-cell atlas of fibrotic skin diseases in this study. In addition, we explored the function of Th17 cell-fibroblast interaction in skin fibrosis. These findings will help to understand fibrotic skin disease pathogenesis in depth and identify potential targets for fibrotic skin disease treatment.

Computational design, expression, and characterization of a Plasmodium falciparum multi-epitope, multi-stage vaccine candidate (PfCTMAG).

Malaria, a tropical disease, claims the lives of thousands of people annually and the development of resistance to insecticides and antimalarial drugs poses a great challenge to current prevention and control strategies. Current malaria vaccines are limited in efficacy, duration of protection, and safety, due to the high antigenic diversity and complex life cycle of the Plasmodium parasite. This study sought to design and assess a more effective multi-stage, multi-epitope vaccine candidate for the control of malaria. A multi-epitope malaria vaccine candidate was designed in silico using multiple antigens from both the pre-erythrocytic and erythrocytic stages, expressed in bacteria, and its sero-reactivity to antibodies in plasma from malaria-positive (cases) and negative individuals (controls) was assessed using enzyme-linked immunosorbent assay (ELISA). Immunization experiments were equally conducted with BALB/c mice. In-silico analysis revealed that the designed antigen, PfCTMAG (Plasmodium falciparum Circumsporozoite, Thrombospondin-related adhesion protein, Merozoite surface protein 2, Apical asparagine (Asn)-rich protein and Glutamate-Rich Protein), effectively bound to Toll-like receptor 4 (TLR-4) and triggered a strong immune response. In sero-reactivity studies, malaria-positives (cases) had higher anti-PfCTMAG IgG ( p =0.024) and IgM ( p<0.001) levels compared to malaria negatives (controls). The mice immunized with PfCTMAG did not show adverse reactions and had higher levels of IgG antibodies (p=0.002) compared to controls, thereby validating the safety and immunogenicity of PfCTMAG as a promising vaccine candidate.

Allosteric Changes Underlie the Outside-In Transmission of Activatory Signals in the TCR.

Rather than being contained in a single polypeptide, and unlike receptor tyrosine kinases, the T cell receptor (TCR) divides its signaling functions among its subunits: TCRα/β bind the extracellular ligand, an antigenic peptide-MHC complex (pMHC), and the CD3 subunits (CD3γ, CD3δ, CD3ε, and CD3ζ) transmit this information to the cytoplasm. How information about the quality of pMHC binding outside is transmitted to the cytoplasm remains a matter of debate. In this review, we compile data generated using a wide variety of experimental systems indicating that TCR engagement by an appropriate pMHC triggers allosteric changes transmitted from the ligand-binding loops in the TCRα and TCRβ subunits to the cytoplasmic tails of the CD3 subunits. We summarize how pMHC and stimulatory antibody binding to TCR ectodomains induces the exposure of a polyproline sequence in the CD3ε cytoplasmic tail for binding to the Nck adapter, the exposure of the RK motif in CD3ε for recruiting the Lck tyrosine kinase, and the induced exposure and phosphorylation of tyrosine residues in all the CD3 cytoplasmic tails. We also review the yet incipient data that help elucidate the structural basis of the Active and Resting conformations of the TCR.

IgG-Mediated Food Intolerance in a Patient with Allergic Symptoms, Acne and Obesity - Effect of Elimination Diet

BACKGROUND: Although the association of food-specific IgG with the development and progression of specific diseases has been shown by many studies, strong correlations are still under question. Are these antibodies a normal immune response to foods, or is the pathogenetic mechanism triggered in another way? Why do elimination diets improve, in many studies, different diseases at different ages? CASE PRESENTATION: We will present the case of a patient who experienced significant improvement in allergic symptoms and reduced body weight by implementing an elimination diet. Type III hypersensitivity reactions are associated with IgG antibodies. They are considered to be normal reactions to food antigens. They are absorbed into the bloodstream in small amounts. However, immediately after a meal, antibodies and food antigen complexes bound to specific IgG circulate in the serum, rapidly cleared by a healthy immune system, specifically the reticuloendothelial system. If large amounts of antibodies are produced and immune complexes are deposited in the blood vessels of various organs and organ systems, various manifestations may occur. CONCLUSION: This is a new field of medicine. Further research, better-standardized tests, and much more extensive studies are needed to prove how to utilize the IgG antibody-based elimination diet properly.

Method for rapid detection of recombinant protein E of West Nile virus

It was noted that the detection time of West Nile virus protein E by standard methods – immunoenzyme assay for West Nile virus antigen, antibody seroconversion, polymerase chain reaction with reverse transcription, virus isolation and neutralization assay, is at least one hour. West Nile virus (genus Flavivirus) belongs to the Japanese encephalitis antigenic complex of the family Flaviviridae and is capable of causing West Nile fever or severe West Nile disease. To increase the detection rate of recombinant protein E of West Nile virus, an express detection method using the developed promising biosensor-based analytical device was proposed. The biosensor is based on a field-effect transistor fabricated by optical lithography using silicon-on-insulator technology. The biosensor design was modernized – the topology of the crystal was changed (one ground electrode was formed in the center, around which 20 field-effect transistors are located), and the crystal surface was additionally covered with a hafnium oxide layer to stabilize the electrical characteristics. Protein detection by means of the biosensor is based on the measurement of current amplitude in the source-to-source circuit of the biosensor with monoclonal antibodies immobilized on the surface of its gate in response to the appearance of the antigen – recombinant protein E of West Nile virus – in the analyzed sample. It was experimentally established that the biosensor is capable of detecting protein concentration of 10 pg/μl. It is necessary to continue further studies to determine the error of measured concentrations and statistical reliability of the results obtained by the biosensor.

Association between human leukocyte antigen class II-DR-DQ and narcolepsy: a case control study.

Narcolepsy is a neurologic disorder characterized by irresistible sleep attacks. Although its etiology is unknown, it is strongly associated with genetic variances in the human leukocyte antigen (HLA) complex. We investigated the association of HLA class II-DR-DQ alleles in a sample of patients with narcolepsy-cataplexy (narcolepsy type 1 [NT1]) and patients with narcolepsy without cataplexy (narcolepsy type 2) with a control group. Additionally, we compared demographic, clinical, and laboratory characteristics of patients with narcolepsy with or without the DQB1*06:02 allele. This case control study included 21 patients with NT1 (56.8%), 16 patients with narcolepsy type 2 (43.2%), and 100 controls. Sequence-based typing identified HLA-DRB1 alleles, and HLA-DQB1 typing was done using polymerase chain reaction (PCR)-sequence-specific oligonucleotide. Allele and haplotype frequencies were calculated by direct counting. Nocturnal polysomnography and Multiple Sleep Latency Test were performed in all participants. In the NT1 group, only 1 allele had a significantly higher frequency than in the narcolepsy type 2 group: DQB1*06:02 (61.9% vs 18.8%). Compared to controls, DQB1*06:02 (61.9% vs 18.0% in controls) and DRB1*15:01 (47.6% vs 8.0%), had higher frequencies in patients with NT1. Multiple analyses showed that patients with NT1 had an increased chance of being HLA-DQB1*06:02 positive. HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 haplotype is associated with NT1 in our Brazilian patients. Polysomnography was identified in DQB1*06:02 positive subgroup rapid eye movement sleep latency ≤ 15 minutes, and all patients had 2 or more sleep-onset rapid eye movement periods at Multiple Sleep Latency Test. This study showed a strong association between HLA-DQB1*06:02 and the haplotype HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 in patients with NT1. Patients with DQB1*0602 allele showed shorter rapid eye movement sleep latencies at polysomnography. These results reinforce the suggestion of DQB1 genotyping as relevant to narcolepsy screening. Bacelar A, Fernandez O, Paradella E, Rodrigues RN, de Castro Moreno CR, Alvarenga R. Association between human leukocyte antigen class II-DR-DQ and narcolepsy: a case control study. J Clin Sleep Med. 2024;20(12):1945-1953.

Unveiling cross-reactivity: implications for immune response modulation in cancer.

Antigen recognition by CD8+ T-cell receptors (TCR) is crucial for immune responses to pathogens and tumors. TCRs are cross-reactive, a single TCR can recognize multiple peptide-Human Leukocyte Antigen (HLA) complexes. The study of cross-reactivity can support the development of therapies focusing on immune modulation, such as the expansion of pre-existing T-cell clones to fight pathogens and tumors. The peptide-HLA (pHLA) surface has previously been used to identify TCR cross-reactivities. In the present work, we sought to perform a comprehensive analysis of peptide-HLA by selecting thousands of human and viral epitopes. We profit from established docking models to identify features from different spatial perspectives of HLA-A*02:01, explore similarities between self and non-self epitopes, and list potential cross-reactive epitopes of therapeutic interest. A total of 2631 unique epitopes from representative viral proteins or human proteins were modeled. We were able to demonstrate that cross-reactive CDR3 sequences from public databases recognize epitopes with similar electrostatic potential, charge, and spatial location. Using data from published studies that measured T-cell reactivity to mutated epitopes, we observed a negative correlation between epitope dissimilarity and T-cell activation. Most analysed cancer epitopes were more similar to self epitopes, yet we identified features distinguishing those more similar to viral antigens. Finally, we enumerated potential cross-reactivities between tumoral and viral epitopes and highlighted some challenges in their identification for therapeutic use. Moreover, the thousands of peptide-HLA complexes generated in our work constitute a valuable resource to study T-cell cross-reactivity.

B cell adapter for PI 3-kinase (BCAP) coordinates antigen internalization and trafficking through the B cell receptor.

B cell adapter for PI 3-kinase (BCAP) is an adaptor molecule associated with signaling through multiple immune receptors, including the B cell receptor (BCR). However, B cell-intrinsic role of BCAP in antibody responses is unclear. We investigated the role of BCAP in B cell response to viral particles and found a previously unidentified mechanism by which BCAP regulates antigen-specific responses. B cell-specific deletion of BCAP in mice leads to decreases in antigen-specific responses through defects in BCR-antigen endocytosis. BCAP is necessary to orchestrate actin reorganization around the antigen for efficient endocytosis through BCR and intracellular processing of antigens. Therefore, loss of BCAP from B cells leads to defects in antigen endocytosis, hampering the propagation of antigen-derived signals and decreasing the ability of B cells to present antigens to T cells. Thus, our study clarifies how BCAP regulates B cell responses to complex antigens and elucidates that antigen positioning inside B cells determines different B cell activation outcomes.

Allorecognition Unveiled: Integrating Recent Breakthroughs Into the Current Paradigm.

In transplantation, genetic differences between donor and recipient trigger immune responses that cause graft rejection. Allorecognition, the process by which the immune system discriminates allogeneic grafts, targets major histocompatibility complex (MHC) and minor histocompatibility antigens. Historically, it was believed that allorecognition was solely mediated by the recipient's adaptive immune system recognizing donor-specific alloantigens. However, recent research has shown significant roles for innate immune components, such as lymphoid and myeloid cells, which are sometimes triggered by the mere absence of a self-protein in the graft. This review integrates recent breakthroughs into the current allorecognition paradigm based on the well-established direct and indirect pathways, emphasizing the semi-direct pathway where recipient antigen-presenting cells (APCs) acquire donor MHC molecules, and the inverted direct pathway where donor CD4+ T cells within the graft activate recipient B cells to produce donor-specific antibodies (DSAs). The review also explores the role of natural killer (NK) cells in both promoting and inhibiting graft rejection, highlighting their dual role in innate allorecognition. Additionally, it discusses the emerging understanding of myeloid cell-mediated allorecognition and its implications for initiating adaptive immune responses. These insights aim to provide a more comprehensive understanding of allorecognition, potentially leading to improved transplant outcomes.

Oceanic Breakthroughs: Marine-Derived Innovations in Vaccination, Therapy, and Immune Health.

The vast, untapped potential of the world's oceans is revealing groundbreaking advancements in human health and vaccination. Microalgae such as Nannochloropsis spp. and Dunaliella salina are emerging as resources for recombinant vaccine development with specific and heterologous genetic tools used to boost production of functional recombinant antigens in Dunaliella salina and Nannochloropsis spp. to induce immunoprotection. In humans, several antigens produced in microalgae have shown potential in combating diseases caused by the human papillomavirus, human immunodeficiency virus, hepatitis B virus, influenza virus, Zika virus, Zaire Ebola virus, Plasmodium falciparum, and Staphylococcus aureus. For animals, microalgae-derived vaccine prototypes have been developed to fight against the foot-and-mouth disease virus, classical swine fever virus, vibriosis, white spot syndrome virus, and Histophilus somni. Marine organisms offer unique advantages, including the ability to express complex antigens and sustainable production. Additionally, the oceans provide an array of bioactive compounds that serve as therapeutics, potent adjuvants, delivery systems, and immunomodulatory agents. These innovations from the sea not only enhance vaccine efficacy but also contribute to broader immunological and general health. This review explores the transformative role of marine-derived substances in modern medicine, emphasizing their importance in the ongoing battle against infectious diseases.

Structural insights into epitope-paratope interactions of a monoclonal antibody targeting CEACAM5-expressing tumors

Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) are overexpressed in some tumor types. The antibody-drug conjugate tusamitamab ravtansine specifically recognizes the A3-B3 domains of human CEACAM5 (hCEACAM5). To understand this specificity, here we map the epitope-paratope interface between the A3-B3 domains of hCEACAM5 (hCEACAM5A3-B3) and the antigen-binding fragment of tusamitamab (tusa Fab). We use hydrogen/deuterium exchange mass spectrometry to identify the tusa Fab paratope, which involves heavy chain (HC) residues 101–109 and light chain residues 48–54 and 88–104. Using surface plasmon resonance, we demonstrate that alanine variants of HC residues 96–108 abolish binding to hCEACAM5, suggesting that these residues are critical for tusa-Fab–antigen complex formation. The cryogenic electron microscopy structure of the hCEACAM5A3-B3- tusa Fab complex (3.11 Å overall resolution) reveals a discontinuous epitope involving residues in the A3-B3 domains and an N-linked mannose at residue Asn612. Conformational constraints on the epitope-paratope interface enable tusamitamab to target hCEACAM5A3-B3 and distinguish CEACAM5 from other CEACAMs.

Discovery of Therapeutic Antibodies Targeting Complex Multi-Spanning Membrane Proteins.

Complex integral membrane proteins, which are embedded in the cell surface lipid bilayer by multiple transmembrane spanning polypeptides, encompass families of proteins that are important target classes for drug discovery. These protein families include G protein-coupled receptors, ion channels, transporters, enzymes, and adhesion molecules. The high specificity of monoclonal antibodies and the ability to engineer their properties offers a significant opportunity to selectively bind these target proteins, allowing direct modulation of pharmacology or enabling other mechanisms of action such as cell killing. Isolation of antibodies that bind these types of membrane proteins and exhibit the desired pharmacological function has, however, remained challenging due to technical issues in preparing membrane protein antigens suitable for enabling and driving antibody drug discovery strategies. In this article, we review progress and emerging themes in defining discovery strategies for a generation of antibodies that target these complex membrane protein antigens. We also comment on how this field may develop with the emerging implementation of computational techniques, artificial intelligence, and machine learning.

Long Non-Coding RNA HCP5 Affects Ferroptosis in Lung Adenocarcinoma through miR-17-5p/HOXA7 Axis.

Ferroptosis, a regulated cell death initiated by Fe-dependent lipoperoxidation, is closely linked to the development of lung adenocarcinoma (LUAD). LncRNA human leukocyte antigen complex P5 (HCP5) has been confirmed as oncogenic in LUAD, but its function in ferroptosis is unknown. Based on the previous bioinformatics mining of the ceRNA (competitive endogenous RNA) network HCP5/miR-17-5p/ Homeobox A7 (HOXA7) related to ferroptosis in LUAD, in this study, we characterized the cell-based experiments to validate the binding between the HCP5/miR-17-5p/HOXA7 axis and ferroptosis. The HCP5/miR-17-5p/HOXA7 linkage was identified by a two-luciferase reporter. Cell Counting Kit-8 (CCK-8) and Transwell assay were employed for the detection of viability, invasion, and migration of A549 cells, respectively. ACSL4 and SLC7A11 were associated with ferroptosis, MMP 9, vimentin, and E-cadherin, which were associated with migration and invasion and were assessed by WB and qRT-PCR. Fe2+ and malondialdehyde (MDA) were analyzed using kits. Over-expression of HCP5 enhances the growth, invasion, and migration of A549 cells by adjusting miR-17-5P to increase the expression of HOXA7. In addition, the knock-down of HCP5 elevated miR-17-5p, which inhibited HOXA7 expression and suppressed ferroptosis and EMT in A549 cells. HCP5/miR-17-5p/HOXA7 can affect ferroptosis as well as the biological behavior of A549 cells.

Load-based divergence in the dynamic allostery of two TCRs recognizing the same pMHC.

Increasing evidence suggests that mechanical load on the αβ T cell receptor (TCR) is crucial for recognizing the antigenic peptide-loaded major histocompatibility complex (pMHC) molecule. Our recent all-atom molecular dynamics (MD) simulations revealed that the inter-domain motion of the TCR is responsible for the load-induced catch bond behavior of the TCR-pMHC complex and peptide discrimination. To further examine the generality of the mechanism, we perform all-atom MD simulations of the B7 TCR under different conditions for comparison with our previous simulations of the A6 TCR. The two TCRs recognize the same pMHC and have similar interfaces with pMHC in crystal structures. We find that the B7 TCR-pMHC interface stabilizes under ~15-pN load using a conserved dynamic allostery mechanism that involves the asymmetric motion of the TCR chassis. However, despite forming comparable contacts with pMHC as A6 in the crystal structure, B7 has fewer high-occupancy contacts with pMHC during the simulation. These results suggest that the dynamic allostery common to the TCRαβ chassis can amplify slight differences in interfacial contacts into distinctive mechanical responses and potentially nuanced biological outcomes.

Double-camouflaged tellurium nanoparticles for enhanced photothermal immunotherapy of tumor

The photothermal conversion properties of tellurium (Te) nanoparticles have been extensively investigated, rendering them a promising candidate for tumor photothermal therapy. However, there is still room for improvement in the development of efficient Te-based drug delivery systems. Here, Te nanoparticles are mineralized with bioactive molecules within attenuated Salmonella (S-Te), which are subsequently taken up by macrophages (RAW264.7) to construct a double-camouflaged delivery platform (RS-Te). Remarkably, RS-Te retains superior photothermal properties under near-infrared irradiation. The mineralization process eliminates bacterial proliferation potential, thereby mitigating the risk of excessive bacterial growth in vivo. Furthermore, the uptake of bacteria by macrophages not only polarizes them into M1 macrophages to induce an anti-tumor immune response but also circumvents any adverse effects caused by complex antigens on the bacterial surface. The results show that RS-Te can effectively accumulate and retain in tumors. RS-Te-mediated photothermal immunotherapy largely promotes the maturation of dendritic cells and priming of cytotoxic T cells induced by near-infrared laser irradiation. Moreover, RS-Te can switch the activation of macrophages from an immunosuppressive M2 phenotype to a more inflammatory M1 state. The double-camouflaged delivery system may offer highly efficient and safe cancer treatment.

The clinical value of serum long non-coding RNA human leukocyte antigen complex group 11/microRNA-532-3p in the diagnosis and prognosis of patients with acute myocardial infarction undergoing percutaneous coronary intervention

BackgroundAcute myocardial infarction (AMI) is a cardiovascular disease with the highest morbidity and mortality rate in the world. Several studies have suggested that abnormal regulation of non-coding RNAs (ncRNAs) may play a vital role in the occurrence and progress of AMI.ObjectiveThe purpose of this study was to investigate the clinical values of human leukocyte antigen complex group 11 (HCG11) or miR-532-3p in the diagnosis and prognosis of patients with AMI after percutaneous coronary intervention (PCI).MethodsThe clinical data of 100 AMI patients who underwent PCI were analyzed retrospectively. According to whether major adverse cardiovascular events (MACE) occurred after PCI, they were divided into MACE group (n = 38) and non-MACE group (n = 62). Basic clinical data and serum HCG11 and miR-532-3p levels were analyzed. Multivariate Cox regression analysis was performed to evaluate the risk factors for MACE, and the receiver operator characteristic (ROC) curve was constructed to assess the clinical predictive value of HCG11 and miR-532-3p for MACE.ResultsCompared with the control group, the serum HCG11 level and miR-532-3p in AMI patients were significantly increased or decreased, and the serum levels of HCG11 and miR-532-3p in the MACE group were significantly increased and decreased, compared with those in non-MACE group. Multivariate Cox regression showed that HCG11 and miR-532-3p were risk factors for MACE occurrence. ROC curve investigated that HCG11 combined with miR-532-3p has accurate predictive value for MACE.ConclusionThis study showed that serum HCG11 and miR-532-3p have certain predictive value for MACE after PCI in patients with AMI.

Regulation of the cell surface expression of classical and non-classical MHC proteins by the human cytomegalovirus UL40 and rhesus cytomegalovirus Rh67 proteins.

The protective immune response induced by a rhesus cytomegalovirus (RhCMV)-vectored simian immunodeficiency virus (SIV) vaccine in rhesus macaques depends on the presence of the viral Rh67 gene in the vaccine. The Rh67 protein contains a peptide that allows the RhCMV-infected cells to maintain expression of major histocompatibility complex (MHC) antigen E at the cell surface. We show that production of this peptide, referred to as "VL9," mirrors that of the equivalent peptide present in the human cytomegalovirus (CMV) protein UL40, despite the little sequence similarity between the two CMV proteins. We also show that the mature UL40 and Rh67 proteins, which have no previously described function, also contribute to CMV immune evasion by reducing cell surface expression of MHC proteins important for the immune system to detect infected cells. Despite these similarities, our work also reveals possible differences between Rh67 and UL40, and these may have implications for the use of human CMV as the vector for a potential HIV-1 vaccine.

NeoaPred: a deep-learning framework for predicting immunogenic neoantigen based on surface and structural features of peptide-human leukocyte antigen complexes.

Neoantigens, derived from somatic mutations in cancer cells, can elicit anti-tumor immune responses when presented to autologous T cells by human leukocyte antigen. Identifying immunogenic neoantigens is crucial for cancer immunotherapy development. However, the accuracy of current bioinformatic methods remains unsatisfactory. Surface and structural features of peptide-HLA class I (pHLA-I) complexes offer valuable insight into the immunogenicity of neoantigens. We present NeoaPred, a deep-learning framework for neoantigen prediction. NeoaPred accurately constructs pHLA-I complex structures, with 82.37% of the predicted structures showing an RMSD of < 1 Å. Using these structures, NeoaPred integrates differences in surface, structural, and atom group features between the mutant peptide and its wild-type counterpart to predict a foreignness score. This foreignness score is an effective factor for neoantigen prediction, achieving an AUROC (Area Under the Receiver Operating Characteristic Curve) of 0.81 and an AUPRC (Area Under the Precision-Recall Curve) of 0.54 in the test set, outperforming existing methods. The source code is released under an Apache v2.0 license and is available at the GitHub repository (https://github.com/Dulab2020/NeoaPred).