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Toward next-generation therapeutic HPV vaccines: A review on expanding the antigen repertoire and an integrated bioinformatics selection framework.

For successful clinical translation of therapeutic human papillomavirus (HPV) vaccines, optimizing antigen selection is key to enhancing eff … tion, and vaccine design. Key selection parameters - including antigen clonality, expression level, major histocompatibility complex (MHC) binding affinity and stability, and immunogenic potential - are critically assessed alongside state-of-the-art computational tools. By proposing standardized selection criteria and optimization strategies, this review aims to provide a roadmap …

Bacterial infection reshapes monocyte and macrophage ontogeny at the CNS borders.

Macrophages in the meninges contribute to immune defense of the central nervous system (CNS), yet their site-specific origin and function re … e ontogeny, increasing monocyte-dendritic cell progenitor-derived monocytes, which expressed higher major histocompatibility complex class II levels and persisted in the brain alongside CD4+ T cells during resolution. Together, these findings reveal dynamic, compartment-specific remodeling of monocyte recruitment and differentiation across CNS borders during bacterial meningoence …

Intestinal epithelial MHC class II induces encephalitogenic CD4 T cells and initiates central nervous system autoimmunity.

The intestinal epithelium plays a critical role in immune-microbiota interactions, yet its contribution to systemic autoimmunity remains unclear. Here, we identify intestinal epithelial cells (IECs) as initiators of experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). In both EAE mice and patients with MS, IECs up-regulate antigen presentation pathways and are associated with increased intestinal T helper 17 (TH17) cell accumulation. Epithelial major histocompatibility complex class II (MHC II) was highly expressed during EAE, particularly in the ileum, a…

Мультиэнштейная геномная ассоциация и мультиомикальный анализ позволяют выявить специфичные особенности многоклерозной генетики.

Множественный склероз (MS) — хроническое воспалительное заболевание центральной нервной системы, характеризующееся обезвоживанием, распространяющимся в пространстве и во времени. Здесь мы провели исследование ассоциации генома (GWAS) с использованием 688 Количество дел, связанных с НР и 205,199 :: контроль со стороны японского населения и выявление важных связей в основном сложном регионе, связанном с гистокомпьютерностью, и в 11q24 году вариант риска, учитывающий специфику населения. С помощью межнаселенных метаанализов GWAS с использованием всего 29,374 случаи и случаи 1,843,563 контроля с 4

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by demyelination disseminated in space and time. Here we performed a genome-wide association study (GWAS) using 688 MS cases and 205,199 controls from the Japanese population and identified significant associations in the major histocompatibility complex reg…

One-dimensional nanosonosensitizer boosted multiple branches of immune responses against MHC-deficient immune-evasive urologic tumor.

Cancer immunotherapies rely on CD8+ cytolytic T lymphocytes (CTLs) in recognition and eradication of tumor cells via antigens presented on major histocompatibility complex class I (MHC-I) molecules. However, we observe MHC-I deficiency in human and murine urologic tumors, posing daunting challenges for successful immunotherapy. We herein report an unprecedented nanosonosensitizer of one-dimensional bamboo-like multisegmented manganese dioxide@manganese-bismuth vanadate (BMMBV) to boost multiple branches of immune responses targeting MHC-I-deficient tumors. BMMBV markedly augments sonodynamic a…

MHC class II+ macrophage differentiation is impaired in metastasized lungs via PGE2 receptor EP2.

Monocytes differentiate into macrophages (Mφs) to facilitate lung metastasis, but the monocyte-to-Mφ transition during this process is not well understood. To investigate, we performed bulk RNA sequencing on Mφs isolated from the lungs of mice bearing Lewis lung carcinoma tumors and from naive lungs. Our results showed impaired differentiation of monocytes into major histocompatibility complex (MHC) class II+ Mφs, with an upregulation of PGE2-inducible genes, including Arg1, in tumor-associated Mφs (TAMs). In vitro experiments confirmed that prostaglandin E2 (PGE2) inhibits the differentiation…

Inborn errors of immunity affecting the MHC class I pathway for antigen presentation.

Inborn errors of immunity affecting the major histocompatibility complex (MHC) class I pathway for antigen presentation represent a rare group of human disease syndromes. Here, we review symptoms associated with such conditions, which manifest as chronic respiratory infections, granulomatous skin lesions, and related severe symptoms. We highlight the potential for misdiagnosis with autoimmune conditions such as granulomatosis with polyangiitis and emphasize the necessity of infection-focused treatment, given the risks associated with immunosuppressive therapy. Furthermore, we present novel lon…

An epitope-directed mRNA vaccine inhibits tumor metastasis through the blockade of MICA/B α1/2 shedding.

Antigenic peptide-based mRNA vaccines have been explored for immunotherapeutic use in various types of cancer because of their advantages in activating durable and specific immune responses. However, their role in modulating tumor metastasis is still unclear. Here, we identify a conserved linear epitope-based peptide, Ma3P, located in the proteolytic region of major histocompatibility complex (MHC) class I-related chain A (MICA) α3 and further design mCM10-L, an mRNA vaccine that encodes the carrier protein CRM197 and 10 tandem repeats of Ma3P. We demonstrate that vaccination with mCM10-L indu…

Trans-ethnic GWAS meta-analysis of idiopathic spermatogenic failure highlights the immune-mediated nature of Sertoli cell-only syndrome.

Non-obstructive azoospermia, a severe form of male infertility caused by spermatogenic failure (SPGF), has a largely unknown genetic basis a … rtoli cell-only (SCO) syndrome, the most extreme SPGF phenotype. The G allele of rs34915133, in the major histocompatibility complex class II region, significantly increases SCO risk (P = 5.25E-10, OR = 1.57), supporting a potential immune-related cause. Additionally, the rs10842262 variant in the SOX5 gene region is also a genetic marker of SCO (P = 5.29E-09, OR = 0.72), highlig …

Blocking plasma cell fate enhances antigen-specific presentation by B cells to boost anti-tumor immunity.

B cells engage in anti-tumor immunity but how they contribute to cancer suppression remains unclear. We report that inhibiting plasma cell differentiation either in IgMi mice lacking Igh elements needed for antibody secretion or in mice with B cell-specific knockout of Blimp-1 (Blimp-1 BcKO) promotes rather than inhibits antitumor immunity and increases numbers of activated B cells. Deficiency of Blimp-1 in tumor-infiltrating B cells generates a unique transcription profile associated with expansion of mutated clones targeting cognate tumor cells. Major histocompatibility complex class II (MHC…

Cathepsin L-dependent positive selection shapes clonal composition and functional fitness of CD4+ T cells.

The physiological significance of thymic positive selection and its reliance on a single stromal cell type, cortical thymic epithelial cells, remain incompletely understood. The lysosomal cysteine protease cathepsin L (CTSL) has been implicated in generating major histocompatibility complex class II-bound peptides in cortical thymic epithelial cells for efficient CD4+ T cell differentiation. Here, we addressed the extent and nature of the CD4+ T cell repertoire changes associated with CTSL deficiency. In the absence of CTSL, a highly selective loss of T cell receptors resulted in a markedly re…

Staphylococcal superantigens evoke temporary and reversible T cell anergy, but fail to block the development of a bacterium specific cellular immune response.

Superantigens (sAgs) are bacterial virulence factors that induce a state of immune hyperactivation by forming a bridge between certain subsets of T cell receptor (TCR) β chains on T lymphocytes, and class II major histocompatibility complex (MHC-II) molecules; this cross-linking leads to indiscriminate T cell activation, cytokine storm and toxic shock. Here we show that sAg exposure drives the preferential expansion of naive and central memory T cell subsets, but not effector or resident memory T cells, which instead, hyper release pro-inflammatory cytokines. A targeted therapeutic approach to…

SARS-CoV-2 NSP5 antagonizes MHC II expression by subverting histone deacetylase 2.

SARS-CoV-2 interferes with antigen presentation by downregulating major histocompatibility complex (MHC) II on antigen-presenting cells, but the mechanism mediating this process is unelucidated. Herein, analysis of protein and gene expression in human antigen-presenting cells reveals that MHC II is downregulated by the SARS-CoV-2 main protease, NSP5. This suppression of MHC II expression occurs via decreased expression of the MHC II regulatory protein CIITA. CIITA downregulation is independent of the proteolytic activity of NSP5, and rather, NSP5 delivers HDAC2 to the transcription factor IRF3…

Animal models of immune-mediated demyelinating polyneuropathies.

Immune-mediated demyelinating polyneuropathies (IMDPs) are rare disorders in which dysregulated adaptive immune responses cause peripheral n … hts on the initial directional cues for peripheral nerve tissue specific autoimmunity using a novel Major Histocompatibility Complex class II conditional knockout mouse strain are also discussed, suggesting an essential research tool to study cell- and time-dependent adaptive immunity in autoimmune diseases.

Integrated Pleiotropic Gene Set Unveils Comorbidity Insights across Digestive Cancers and Other Diseases.

Comorbidities are prevalent in digestive cancers, intensifying patient discomfort and complicating prognosis. Identifying potential comorbid … pleiotropic gene set comprising 548 genes in total. Particularly, there enclosed the genes encoding major histocompatibility complex or related to antigen presentation. Additionally, we have unveiled patterns in protein-protein interactions and key hub genes/proteins including TP53, KRAS, CTNNB1 and PIK3CA, which may elucidate the co-occurrence of digestive cancers with certain d …

Proteogenomic characterization of primary colorectal cancer and metastatic progression identifies proteome-based subtypes and signatures.

Metastatic progression of colorectal adenocarcinoma (CRC) remains poorly understood and poses significant challenges for treatment. To overc … ially in metastatic lesions. Tumor microenvironment analysis shows immune evasion via modulation of major histocompatibility complex (MHC) class I/II and antigen processing pathways. This study characterizes both primary and metastatic CRCs and provides a large proteogenomics dataset of metastatic progression.

IRF8-mutant B cell lymphoma evades immunity through a CD74-dependent deregulation of antigen processing and presentation in MHCII complexes.

The mechanism by which interferon regulatory factor 8 (IRF8) mutation contributes to lymphomagenesis is unknown. We modeled IRF8 variants in B cell lymphomas and found that they affected the expression of regulators of antigen presentation. Expression of IRF8 mutants in murine B cell lymphomas suppressed CD4, but not CD8, activation elicited by antigen presentation and downmodulated CD74 and human leukocyte antigen (HLA) DM, intracellular regulators of antigen peptide processing/loading in the major histocompatibility complex (MHC) II. Concordantly, mutant IRF8 bound less efficiently to the pr…

Thymus antibody-secreting cells possess an interferon gene signature and are preferentially expanded in young female mice.

Antibody-secreting cells (ASCs) are key contributors to humoral immunity through immunoglobulin production and the potential to be long-live … cytometry confirmed that THY ASCs had increased levels of Toll-like receptor 7 as well as CD69 and major histocompatibility complex class II. Overall, we identified fundamental aspects of THY ASC biology which may be leveraged for future in depth studies of this population in both health and disease.

The pre-existing T cell landscape determines the response to bispecific T cell engagers in multiple myeloma patients.

Bispecific T cell engagers (TCEs) have shown promise in the treatment of various cancers, but the immunological mechanism and molecular determinants of primary and acquired resistance to TCEs remain poorly understood. Here, we identify conserved behaviors of bone marrow-residing T cells in multiple myeloma patients undergoing BCMAxCD3 TCE therapy. We show that the immune repertoire reacts to TCE therapy with cell state-dependent clonal expansion and find evidence supporting the coupling of tumor recognition via major histocompatibility complex class I (MHC class I), exhaustion, and clinical re…

Human DUX4 and mouse Dux interact with STAT1 and broadly inhibit interferon-stimulated gene induction.

DUX4 activates the first wave of zygotic gene expression in the early embryo. Mis-expression of DUX4 in skeletal muscle causes facioscapulohumeral dystrophy (FSHD), whereas expression in cancers suppresses IFNγ induction of major histocompatibility complex class I (MHC class I) and contributes to immune evasion. We show that the DUX4 protein interacts with STAT1 and broadly suppresses expression of IFNγ-stimulated genes by decreasing bound STAT1 and Pol-II recruitment. Transcriptional suppression of interferon-stimulated genes (ISGs) requires conserved (L)LxxL(L) motifs in the carboxyterminal …