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Individualized mRNA vaccines evoke durable T cell immunity in adjuvant TNBC.

Triple-negative breast cancer (TNBC) is frequently associated with metastatic relapse, even at an early stage1. Here we assessed an individu … achieved complete remission on subsequent anti-PD-1 therapy; another patient had a tumour with low major histocompatibility complex (MHC) class I expression with MHC class I-deficient cells growing out under vaccination; and the third patient was BRCA-positive and had a recurrence from a genetically distinct primary tumour. These findings demonstrate the feasibility of individua …

Targeting JAK2: Genetic and Pharmacological Inhibition Attenuates Immune-Mediated Liver Injury by Suppressing Proinflammatory Macrophage.

Effective therapeutic targets for immune-mediated liver injury remain insufficient, necessitating the urgent development of novel therapeuti … -deficient mice displayed less mature and activated phenotypes as evidenced by lower expressions of major histocompatibility complex class II (MHC-II), inflammatory marker Ly6C, inflammatory cytokine production, and higher phagocytic capacity, which subsequently resulted in lower levels of CD4+ T cell activation. These findings collectively underscore baricitinib's therapeutic po …

Discovering the Hidden Power of NGLY1: Orchestrating Immune Cell Functions and Autoimmune Diseases.

The enzyme N-glycanase 1 (NGLY1) regulates autophagic processes and endoplasmic reticulum (ER)-associated proteasomal degradation by de-N-gl … mune evasion. Importantly, NGLY1 was shown to process foreign peptides destined for presentation on major histocompatibility complex (MHC) molecules, a process that enables cytotoxic T lymphocytes to identify pathogens or mutated cells. Finally, altered levels of NGLY1 may impair B lymphocytes, especially the formation and function of antibody-secreting cells. In this review, we …

PIKfyve inhibition in MM disrupts autophagy and lysosome function, increasing MHC expression and cholesterol metabolism.

We previously reported a chemogenomics screen that unexpectedly identified phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) as a vulnerab … PIK001 exposure also resulted in significantly increased cholesterol metabolism and upregulation of major histocompatibility complex (MHC) class I expression, with potential implications in tumor immunity. Beyond MM, PIKfyve inhibition also shows selective cytotoxicity in acute myeloid leukemia, melanoma, and renal cancer, highlighting broader therapeutic potential. These finding …

Site-specific neoepitope induction by RNA editing reprograms tumor immunogenicity.

INTRODUCTION: Neoantigens derived from somatic mutations exhibit high immunogenicity and specificity. However, their stochastic nature neces … DAR-based A-to-I RNA editing system to selectively modify T cell receptor (TCR)-contact residues in major histocompatibility complex class I (MHC-I)-presented peptides derived from P1A and AFP. We further evaluated the immunogenicity and antitumor efficacy of lipid nanoparticle-formulated P1A-REISN circular RNA vaccination in immunocompetent BALB/c mice bearing tumors with P1A-RE …

Ex vivo pretreatment with venetoclax boosts antileukemic efficacy of therapeutic γδ T cells in AML models.

Ex vivo engineering strategies for adoptive αβ T cell therapies increasingly use pharmacological modulation to improve survival, expansion, and antitumor activity. Short-term exposure to the B cell lymphoma-2 (BCL-2) inhibitor venetoclax during αβ T cell manufacturing enhances apoptotic priming and effector persistence, suggesting a route to strengthen other T cell lineages. γδ T cells share cytotoxic properties with αβ T cells but recognize targets independently of major histocompatibility complex and show low alloreactivity, supporting off-the-shelf use in acute myeloid leukemia (AML). Wheth…

Characterization of [18F]SMBT-1 binding substrates in Alzheimer's disease and related disorders: A postmortem biochemical and immunohistochemical study.

INTRODUCTION: Neuroimaging studies report associations of amyloid beta (Aβ) positron emission tomography (PET) with [18F](S)-(2-methylpyrid- … 1 autoradiography and MAO-B immunoreactivity in relation to glial fibrillary acidic protein (GFAP), major histocompatibility complex II (MHC-II), Aβ, phosphorylated tau, cyano-Pittsburgh compound B (cyano-PiB), and X-34 on brain sections from AD, non-AD tauopathies, and nondemented controls. RESULTS: [18F]SMBT-1 binding correlated with MAO-B activity and [3H]PiB binding, with hi …

The development of novel chimeric antigen receptor gamma-delta T cells against multiple myeloma and single-cell RNA sequencing analysis.

Chimeric antigen receptor (CAR) gamma-delta (γδ) T cells offer a major histocompatibility complex-independent, off-the-shelf alternative to conventional CAR alpha-beta (αβ) Tcells, but their efficacy in multiple myeloma (MM) remains underexplored. In this work, we developed a series of novel CAR γδ T cells redirected to B-cell maturation antigen (BCMA) and performed functional assays compared to CAR αβ T cells. As a result, novel CAR γδ T cells demonstrated similar activation upon antigen stimulation compared with CAR αβ T cells but showed lower proliferative capacity and less durable cytotoxi…

Phylogenetic analysis of amino acid sequences indicates a central role of transmembrane domain structural elements in MHC class II function.

Human leukocyte antigen class II genes are highly polymorphic. This raises the question of how polymorphisms are distributed across the enti … on of polymorphism within class II and a key role for the TMD and its functional residues/motifs in major histocompatibility complex class II immunobiology.

Elucidating genetic backgrounds of myasthenia gravis in Japanese by genome-wide association studies and multi-omics analyses of thymoma.

Myasthenia gravis (MG) is an autoimmune disorder characterized by impaired neuromuscular transmission and motor symptoms. Its genetic backgr … P = 2.1×10-15), and thymoma-associated gMG (g-TAMG; OR = 1.92, P = 1.1×10-15). Fine-mapping of the major histocompatibility complex region reveal distinct associations of HLA-DRB1 with late onset gMG (g-LOMG) and HLA-A with early onset gMG (g-EOMG). The MG risk TERT lead variant rs2736099 is associated with poor treatment response, especially in g-AChR-Ab(+)MG and g-EOMG (P < 0. …

Non-cytolytic re-engineering of a viral vaccine vector enables durable effector-memory T cell immunity by reinforcing type I IFN induction.

Replication-deficient viral vector systems hold promise for CD8 T cell-based vaccination, but the molecular mechanisms accounting for platfo … n with non-cytolytic viral vectors offered an opportunity for CD8 T cells to integrate peptide-MHC (major histocompatibility complex) and IFN-I signals during priming. These mechanistic insights should help to refine vaccines aimed at eliciting durable and protective effector-memory CD8 T cell immunity.

Expression of MHC I Isoforms in Bovine Placentomes: Impact of Cloning.

Major histocompatibility complex class I (MHC-I) gene expression in the placenta is modulated to tailor the maternal immune response to fetal antigens during pregnancy. This study evaluated MHC-I expression through immunohistochemistry (IHC) using an anti-mouse preimplantation embryo development (PED) clone Qa-2 and anti-bovine leukocyte antigen I (BoLA) monoclonal antibody clone IL-A88 (n = 23), as well as RT-qPCR (n = 17) for classical and non-classical (BoLA-NC) genes in control and cloned bovine placentomes during early and near-term gestation. Control samples showed minimal Qa-2 protein e…

Computational identification of B and T-cell epitopes for designing a multi-epitope vaccine against SARS-CoV-2 spike glycoprotein.

Although the peak of the COVID-19 pandemic has passed, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose a sign … igate interactions between the vaccine and key immune components, including Toll-like receptors and major histocompatibility complex molecules. Stability of these interactions was confirmed using molecular dynamics simulations in triplicate, conducted over 100 ns using GROMACS 2023 to compute key metrics, such as root mean square deviation, root mean square fluctuation, solvent-a …

Epigenetically modulating macrophage subpopulations to promote long-term allograft survival in a mouse heart transplant model.

Despite much-improved protocols that broadly suppress the adaptive immune cells, most allografts are still lost to chronic rejection, in whi … etion of Brd4 in myeloid cells profoundly inhibited the induction of M2 cells. Moreover, in a fully major histocompatibility complex-mismatched heart transplant model, in which treatment with cytotoxic T lymphocyte antigen-4 Ig fusion protein led to the development of chronic rejection, inhibition of BDR4 in transplant recipients resulted in long-term heart allograft survival, wh …

Natural killer cells in kidney immune surveillance, injury and fibrosis.

Natural killer (NK) cells are cytotoxic lymphocytes of the innate immune system with essential roles in immune surveillance, tissue homeostasis and inflammation. In the kidney, NK cells comprise a heterogeneous population that includes both circulating and tissue-resident subsets, each shaped by environmental cues and genetic factors through interactions with major histocompatibility complex class I molecules. The latest research data highlight multifaceted NK cell contributions to kidney physiology and pathology. In steady state, NK cells support kidney immune surveillance and crosstalk with …

In silico screening and identification of CTL and HTL epitopes in the secreted virulence factors of Mycobacterium tuberculosis.

BACKGROUND: Mycobacterium tuberculosis (MTb) is a highly infectious pathogen and a global health threat due to its resilient cell wall and i … age was estimated for the Southeast Asian (SEA) region. Selected epitopes were also docked to their major histocompatibility complex alleles. RESULTS: Five secretory proteins critical to MTb pathogenesis and virulence were identified as antigenic (antigenicity score > 0.4). Predicted epitopes had IC50 values ≤ 500 nM, indicating strong binding affinity, with an estimated 94% pop …

Swine Xenografts Share Few Predicted Indirectly Recognisable SLA-Derived Epitopes With HLA-Derived Epitopes From Human Kidney Grafts.

Swine-derived kidneys are a promising alternative organ source for transplantation, but compatibility in the major histocompatibility complex remains an immunological barrier. Furthermore, in repeat transplantations, CD4+ memory T cells can lead to a more rapid immune response against repeated exposure to the same antigens. Several studies have shown that HLA and SLA proteins share overlapping B cell epitopes due to structural or electrostatic similarities, but the role of overlapping T cell epitopes has not been fully explored. This study aims to computationally analyse the potential risk of …

Proviruses in CD4+ T cells reactive to autologous antigens contribute to nonsuppressible HIV-1 viremia.

Antiretroviral therapy (ART) halts human immunodeficiency virus-1 (HIV-1) replication, reducing plasma virus concentrations to below the lim … nstrate that stimulation of CD4+ T cells with autologous cell lysates induced virus production in a major histocompatibility complex class II-dependent manner. In seven of eight participants with NSV, we recovered viral RNA released ex vivo in response to autologous cell lysates that matched plasma virus. This process involved both defective and replication-competent proviruses r …

Пренебрежение двойной ролью билирубина в неврологических болезнях: всеобъемлющее исследование его нейрозащитного и нейротоксичного воздействия.

Нейродегенеративные расстройства характеризуются постепенной потерей нейронов, что приводит к значительным сбоям в работе двигателей и когнитивных систем. Bilirubin — побочный продукт гема желтого цвета, существующий в двух первичных изоформах, а именно в неокончательных и спаренных, в то время как первоначально произведенный неокончательный изомер является липофильным и цитотоксичным по своей природе. На физиологическом уровне билирубин играет важную роль в функционировании мозга, выступая в качестве мощного антиоксиданта, предотвращая окислительное повреждение тканей головного мозга путем ус

Совпадение в аннотации оригинала
Neurodegenerative disorders are characterized by a progressive loss of neurons, causing substantial deficits in motor and cognitive function … ine release, complement system interception, fragment crystallization (Fc) receptor modulation, and major histocompatibility complex (MHC II) expression modification, which lower the risk of inflammatory and autoimmune reactions in the central nervous system (CNS). As per the literature, serum bilirubin concentrations are associated with CNS diseases such as Alzheimer's disease ( …

Preexisting Skin-Resident CD8 and γδ T-cell Circuits Mediate Immune Response in Merkel Cell Carcinoma and Predict Immunotherapy Efficacy.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with a ∼50% response rate to immune checkpoint blockade (ICB) therap … sponse. We identified CD8 Trm and Vδ1 T cells as clinically actionable mediators of ICB response in major histocompatibility complex-high and -low MCCs, respectively.