Geometric deep learning improves generalizability of MHC-bound peptide predictions.

The interaction between peptides and major histocompatibility complex (MHC) molecules is pivotal in autoimmunity, pathogen recognition and tumor immunity. Recent advances in cancer immunotherapies demand for more accurate computational prediction of MHC-bound peptides. We address the generalizability challenge of MHC-bound peptide predictions, revealing limitations in current sequence-based approaches.

Induction of broad multifunctional CD8+ and CD4+ T cells by hepatitis B virus antigen-based synthetic long peptides .

Introduction: Therapeutic vaccination based on synthetic long peptides (SLP) containing both CD4+ and CD8+ T cell epitopes is a promising treatment strategy for chronic hepatitis B infection (cHBV).

Methods: We designed SLPs for three HBV proteins, HBcAg and the non-secreted proteins polymerase and X, and investigated their ability to induce T cell responses . A set of 17 SLPs was constructed based on viral protein conservation, functionality, predicted and validated binders for prevalent human leukocyte antigen (HLA) supertypes, validated HLA I epitopes, and chemical producibility.

Hepatitis E virus infection activates NOD-like receptor family pyrin domain-containing 3 inflammasome antagonizing interferon response but therapeutically targetable.

Background And Aims: HEV infection is the most common cause of liver inflammation, but the pathogenic mechanisms remain largely unclear. We aim to explore whether HEV infection activates inflammasomes, crosstalk with antiviral interferon response, and the potential of therapeutic targeting.

Approach And Results: We measured IL-1β secretion, the hallmark of inflammasome activation, in serum of HEV-infected patients and rabbits, and in cultured macrophage cell lines and primary monocyte-derived macrophages.

Empirical Evaluation of the Use of Computational HLA Binding as an Early Filter to the Mass Spectrometry-Based Epitope Discovery Workflow.

Immunopeptidomics is used to identify novel epitopes for (therapeutic) vaccination strategies in cancer and infectious disease. Various false discovery rates (FDRs) are applied in the field when converting liquid chromatography-tandem mass spectrometry (LC-MS/MS) spectra to peptides. Subsequently, large efforts have recently been made to rescue peptides of lower confidence.

The Potential of Soluble Human Leukocyte Antigen Molecules for Early Cancer Detection and Therapeutic Vaccine Design.

Human leukocyte antigen (HLA) molecules are essential for anti-tumor immunity, as they display tumor-derived peptides to drive tumor eradication by cytotoxic T lymphocytes. HLA molecules are primarily studied as peptide-loaded complexes on cell membranes (mHLA) and much less attention is given to their secretion as soluble HLA-peptide complexes (sHLA) into bodily fluids. Yet sHLA levels are altered in various pathologies including cancer, and are thus of high interest as biomarkers.

The relation of brain ouabain-like compounds and idiopathic intracranial hypertension.

Objectives: To determine the relationship between levels of ouabain-like compounds (OLC) in the cerebrospinal fluid (CSF) and the occurence of idiopathic intracranial hypertension (IIH).

Background: OLC are naturally occurring inhibitors of the sodium-potassium ATPase that are found in the CSF of mammals. Since the production of CSF is dependent upon sodium-potassium ATPase activity, and since there is evidence that the increased intracranial pressure found in the condition of IIH may be the result of increased CSF production, we hypothesized that the level of endogenous OLC would be reduced in the CSF of patients with IIH.

Primary care physicians' attitudes about obesity and its treatment.

Objective: This study was designed to assess physicians' attitudes toward obese patients and the causes and treatment of obesity.

Research Methods And Procedures: A questionnaire assessed attitudes in 2 geographically representative national random samples of 5000 primary care physicians. In one sample (N = 2500), obesity was defined as a BMI of 30 to 40 kg/m(2), and in the other (N = 2500), obesity was defined as a BMI > 40.