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Background Chinese woodchucks ( M. himalayana ) were recently found to be susceptible to woodchuck hepatitis virus (WHV) infection. In this study, we aimed to determine the susceptibility to WHV infection of M. himalayana from different areas and their association with the animal genetic background exemplified by cytochrome B and MHC-DRB molecules. Methods Animals from four different areas in Qinghai province were inoculated with WHV59 strains. The virological markers including WHV surface antigen (WHsAg), WHV core antibody (WHcAb), and WHV DNA in serum were measured by ELISA and Real-time PCR, respectively. The sequences of cytochrome B gene and MHC-DRB molecules were obtained and sorted with Clustalx software. The nucleotide variation sites were identified using MEGA5 software. Results The animals from four different areas had different susceptibility to WHV infection. Animals from TR and TD areas had a high level of long-lasting viremia, while those from GD and WL areas had a low level of transient viremia after WHV inoculation. All of the animals belong to the same subspecies M. himalayana robusta identified by cytochrome B gene sequences. Based on their nucleotide variation pattern, 8 alleles of cytochrome B gene were identified, and 7 MHC-DRB alleles were identified. Allele A of cytochrome B and Allele Mamo-DRB1*02 of MHC-DRB was found to be frequent in animals from TR and TD areas, while Allele H of cytochrome B and Allele Mamo-DRB1*07 of MHC-DRB was predominant in animals from GD and WL areas. Conclusion Chinese woodchucks from different areas differed in their susceptibility to WHV infection, though they belong to the same subspecies M. himalayana robusta . The genetic background exemplified by cytochrome B and MHC-DRB differed in Chinese woodchucks with different susceptibility to WHV infection.

The immune responses of type 2 T helper cells (Th2) play an important role in asthma and promote the differentiation of alternatively activated (M2) macrophages. M2 macrophages have been increasingly understood to contribute to Th2 immunity. We hypothesized that M2 macrophages are altered in asthma and modulate Th2 responses. The aim of this study was to characterize the phenotype and function of human monocyte-derived M2 and bronchoalveolar lavage fluid (BALF) macrophages from healthy control subjects and subjects with asthma. Phenotypic characteristics and effector function of M2 macrophages were examined using monocyte-derived and BALF macrophages obtained from subjects with asthma (n = 28) and healthy volunteers (n = 9) by flow cytometry and quantitative PCR. Resting monocyte-derived (M0) and M2 macrophages were generated by the addition of macrophage colony–stimulating factor or macrophage colony–stimulating factor plus IL-4, respectively. M2 macrophage cytokine expression and their impact on dendritic and CD4+ T cell activation were examined in vitro. High levels of CD206 and major histocompatibility complex class II expression identify macrophages with an M2 phenotype that are increased 2.9-fold in the BALF of subjects with asthma compared with control subjects. M2 macrophages have elevated IL-6, IL-10, and IL-12p40 production compared with conventional macrophages and modulate dendritic and CD4+ T cell interactions. Histamine receptor 1 and E-cadherin expression identify M2 macrophage subsets associated with increased airflow obstruction. M2 macrophages have a distinct cell surface and effector phenotype and are found in increased numbers in subjects with asthma. These findings suggest that M2 macrophages may play an important role in allergic asthma through their bidirectional interactions with immune and structural cells, and inflammatory mediators.

The liver is a very tolerogenic organ. It is continually exposed to a multitude of antigens and is able to promote an effective immune response against pathogens and simultaneously immune tolerance against self-antigens. In spite of strong peripheral and central tolerogenic mechanisms, loss of tolerance can occur in autoimmune liver diseases, such as autoimmune hepatitis (AIH) through a combination of genetic predisposition, environmental factors, and an imbalance in immunological regulatory mechanisms. The liver hosts several types of conventional resident antigen presenting cells (APCs) such as dendritic cells, B cells and macrophages (Kupffer cells), and unconventional APCs including liver sinusoidal endothelial cells, hepatic stellate cells and hepatocytes. By standard (direct presentation and cross-presentation) and alternative mechanisms (cross-dressing and MHC class II-dressing), liver APCs presents self-antigen to naive T cells in the presence of costimulation leading to an altered immune response that results in liver injury and inflammation. Additionally, the transport of antigens and antigen:MHC complexes by trogocytosis and extracellular vesicles between different cells in the liver contributes to enhance antigen presentation and amplify autoimmune response. Here, we focus on the impact of antigen presentation on the immune response in the liver and on the functional role of the immune cells in the induction of liver inflammation. A better understanding of these key pathogenic aspects could facilitate the establishment of novel therapeutic strategies in AIH.

Major histocompatibility complex class II (MHC-II) molecules are involved in immune responses against pathogens and vaccine candidates’ immunogenicity. Immunopeptidomics for identifying cancer and infection-related antigens and epitopes have benefited from advances in immunopurification methods and mass spectrometry analysis. The mouse anti-MHC-II-DR monoclonal antibody L243 (mAb-L243) has been effective in recognising MHC-II-DR in both human and non-human primates. It has also been shown to cross-react with other animal species, although it has not been tested in livestock. This study used mAb-L243 to identify Staphylococcus aureus and Salmonella enterica serovar Typhimurium peptides binding to cattle and swine macrophage MHC-II-DR molecules using flow cytometry, mass spectrometry and two immunopurification techniques. Antibody cross-reactivity led to identifying expressed MHC-II-DR molecules, together with 10 Staphylococcus aureus peptides in cattle and 13 S. enterica serovar Typhimurium peptides in swine. Such data demonstrates that MHC-II-DR expression and immunocapture approaches using L243 mAb represents a viable strategy for flow cytometry and immunopeptidomics analysis of bovine and swine antigen-presenting cells.

Major histocompatibility complex class II (MHC II) deficiency (bare lymphocyte syndrome type II) is an autosomal-recessive combined immunodeficiency caused by pathogenic variants in the transcriptional regulators CIITA, RFXANK, RFX5, or RFXAP. While RFXANK founder mutations predominate in North Africa, CIITA-related disease is extremely rare. We report two siblings from a consanguineous Moroccan family with the classic early-infancy phenotype. The elder sister developed recurrent febrile rashes, oral candidiasis, and locoregional BCGitis with acid-fast bacilli in granulomas, followed by progressive respiratory failure and fatal cytomegalovirus pneumonitis despite antiviral therapy; immunology showed profound CD4 + lymphopenia with CD4/CD8 inversion, near-absent HLA-DR on B cells, undetectable IgG/IgA, and elevated IgM. The proband, identified during family follow-up, had recurrent mucocutaneous infections, marked CD4 + lymphopenia with CD4/CD8 inversion, and near-absent HLA-DR on B cells; he was started on monthly intravenous immunoglobulin and trimethoprim–sulfamethoxazole prophylaxis. Targeted next-generation sequencing revealed a novel homozygous nonsense CIITA variant (c.1615C>T; p.R539*), predicted to truncate the GTP-binding domain, abolish downstream leucine-rich repeats, and undergo nonsense-mediated decay, and classified as pathogenic according to ACMG criteria. Molecular confirmation enabled genetic counseling, cascade testing, withholding BCG, and urgent evaluation for allogeneic hematopoietic stem-cell transplantation. This case, likely the first CIITA-related MHC II deficiency reported from Morocco, expands the regional genotypic spectrum and underscores the value of early HLA-DR flow-cytometric assessment and prompt molecular testing in infants from consanguineous families to guide prophylaxis, vaccination decisions, and timely referral for curative therapy.

The incidence of obesity is increasing annually worldwide. A high-fat diet (HFD) causes intestinal barrier damage, but effective interventions are currently unavailable. Our previous work demonstrated the therapeutic effect of nobiletin on obese mice; thus, we hypothesized that nobiletin could reverse HFD-induced damage to the intestinal barrier. Male C57BL/6 J mice were orally administered nobiletin for 14 d. After identification, the obese mice were equally divided into three groups: the HFD group, the low-dose (NOL, 100 mg/kg/d) group and the high-dose nobiletin (NOH, 200 mg/kg/d) group. A normal control group (CON) was also included. Hematoxylin and eosin (HE) staining and immunofluorescence were used to observe the intestinal barrier. RT-qPCR was used to determine the transcriptomic levels of genes involved in intestinal barrier integrity and lipid metabolism. The results revealed that intestinal tight proteins, including ZO-1 and Occludin, were significantly reduced in HFD-fed mice but markedly restored after nobiletin intervention, particularly in NOH mice. Improvements in the intestinal barrier and lipid metabolism associated with major histocompatibility complex class II (MHC-II) and relevant elements were revealed after nobiletin intervention. Enrichment analysis revealed that MHC-II plays an important role in the restoration of the intestinal barrier. Taken together, nobiletin restored intestinal barrier integrity and lipid metabolism by regulating MHC-II expression.

Major Histocompatibility Complex Class II Deficiency is a rare primary immunodeficiency disease with autosomal recessive inheritance. It is characterized by the absence of Major Histocompatibility Complex Class II molecules on the surface of immune cells. In this article, we will present a four-month-old baby girl who presented with recurrent fever and progressive exacerbation of respiratory symptoms since a month ago. Relevant examinations suggested pancytopenia, a decrease in CD4 and CD3 ratio, and CD4/CD8 inversion, hypogammaglobulinemia, and diagnosis of hemophagocytic syndrome during treatment which all led to the consideration of the presence of immunodeficiency diseases, and the diagnosis of Major Histocompatibility Complex Class II Deficiency was made by peripheral blood whole-exon sequencing (WES). This case is remarkable in that it reveals features of hemophagocytic syndrome in a Major Histocompatibility Complex Class II Deficiency infant, most probably caused by cytomegalovirus, which rarely reported before, and the Major Histocompatibility Complex Class II Deficiency caused by a novel mutation site in the RFXANK gene which never reported, and it also describes the diagnostic and therapeutic course in detail. In addition, we have summarized the information related to Major Histocompatibility Complex Class II Deficiency triggered by mutations in the RFXANK gene to assist clinicians in early recognition and diagnosis.

An increase in the life expectancy during the last decades in most world countries has resulted in the growing number of people suffering from neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, fron-totemporal dementia, and others. Familial forms of neurodegenerative diseases account for 5–10% of all cases and are caused by mutations in specific genes often resulting in pathological protein deposition. The risk factors for neurodegeneration include trauma, lifestyle, and allelic variants of disease-associated genes with incomplete penetrance. Many of these gene variants are located in immunity-related loci, particularly in the human leukocyte antigen locus (HLA class II) coding for proteins of the major histocompatibility complex class II (MHCII). HLA class II plays a key role in the antigen presentation and is expressed in microglial cells. Microglia is a component of innate immunity. On the one hand, microglial cells phagocytize pathological protein deposits; on the other hand, they produce proinflammatory factors accelerating neuronal death. The involvement of adaptive immunity mechanisms (antigen presentation, T cell response, antibody production) in the development of neurodegenerative diseases remains unclear and requires further research, including more detailed studies of the role of identified HLA class II genetic variants.

Major histocompatibility complex (MHC)-Associated Peptide Proteomics (MAPPs) is an ex vivo method used to assess the immunogenicity risk of biotherapeutics. MAPPs can identify potential T-cell epitopes within the biotherapeutic molecule. Using adalimumab treated human monocyte derived dendritic cells (DCs) and a pan anti-HLA-DR antibody (Ab), we systematically automated and optimized biotin/streptavidin (SA)-capture antibody coupling, lysate incubation with capture antibody, as well as the washing and elution steps of a MAPPs method using functionalized magnetic beads and a KingFisher Magnetic Particle processor. Automation of these steps, combined with capturing using biotinylated-Ab/SA magnetic beads rather than covalently bound antibody, improved reproducibility as measured by minimal inter-and intra-day variability, as well as minimal analyst-to-analyst variability. The semi-automated MAPPs workflow improved sensitivity, allowing for a lower number of cells per analysis. The method was assessed using five different biotherapeutics with varying immunogenicity rates ranging from 0.1 to 48% ADA incidence in the clinic. Biotherapeutics with ≥10%immunogenicity incidence consistently presented more peptides (1.8-28 fold) and clusters (10-21 fold) compared to those with <10% immunogenicity incidence. Our semi-automated MAPPs method provided two main advantages over a manual workflow- the robustness and reproducibility affords confidence in the epitopes identified from as few as 5 to 10 donors and the method workflow can be readily adapted to incorporate different capture Abs in addition to anti-HLA-DR. The incorporation of semi-automated MAPPs with biotinylated-Ab/SA bead-based capture in immunogenicity screening strategies allows the generation of more consistent and reliable data, helping to improve immunogenicity prediction capabilities in drug development. MHC associated peptide proteomics (MAPPs), Immunogenicity risk assessment, in vitro /ex vivo, biotherapeutics, Major Histocompatibility Complex Class II (MHC II), LC-MS, Immunoaffinity Capture, streptavidin magnetic beads

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by self-antibody production and widespread inflammation affecting various body tissues. This disease is driven by the breakdown of immune tolerance, which promotes the activation of autoreactive B and T cells. A key feature of SLE is dysregulation in antigen presentation, where antigen-presenting cells (APCs) play a central role in perpetuating immune responses. Dendritic cells (DCs) are highly specialized for antigen presentation among APCs. At the same time, myeloid-derived suppressor cells (MDSCs) can also express MHC-II molecules, although their role in SLE is less understood. Utilizing the SLE model, MRL/MpJ-Faslpr/J, we determined the presence of different phenotypes of DCs and MDSCs expressing MHC-II in secondary lymphoid organs, along with the gene expression of ICOSL, CD80 and CD86 in the spleen. Our study determined that the most abundant population of APCs in secondary lymphoid organs corresponds to cDC CD103−CD11b+ MHC-II+ throughout SLE development. Additionally, ICOSL expression increased over time, becoming more preponderant in week 16 in the SLE model, which could indicate that it is a crucial pathway for the development and progression of the pathology. In week 16, we observed a positive correlation between M-MDSC MHC-II and IFN-γ-producing CD4+ T cells.