Characterization of Conserved and Promiscuous Human Rhinovirus CD4 T Cell Epitopes

This research was supported by UCM research special funds to P.A.R. and by the CAM research agency through grant IND2020/BMD-17364 to P.A.R.Human rhinovirus (RV) is the most common cause of upper respiratory infections and exacerbations of asthma. In this work, we selected 14 peptides (6 from RV A and 8 from RV C) encompassing potential CD4 T cell epitopes. Peptides were selected for being highly conserved in RV A and C serotypes and predicted to bind to multiple human leukocyte antigen class II (HLA II) molecules. We found positive T cell recall responses by interferon gamma (IFNγ)-ELISPOT assays to eight peptides, validating seven of them (three from RV A and four from RV C) as CD4 T cell epitopes through intracellular cytokine staining assays. Additionally, we verified their promiscuous binding to multiple HLA II molecules by quantitative binding assays. According to their experimental HLA II binding profile, the combination of all these seven epitopes could be recognized by >95% of the world population. We actually determined IFNγ responses to a pool encompassing these CD4 T cell epitopes by intracellular cytokine staining, finding positive responses in 29 out of 30 donors. The CD4 T cell epitopes identified in this study could be key to monitor RV infections and to develop peptide-based vaccines against most RV A and C serotypes.Depto. de Inmunología, Oftalmología y ORLFac. de MedicinaTRUEComunidad de MadridUniversidad Complutense de Madridpu

Immune Tolerance in the Oral Mucosa

The oral mucosa is a site of intense immune activity, where a large variety of immune cells meet to provide a first line of defense against pathogenic organisms. Interestingly, the oral mucosa is exposed to a plethora of antigens from food and commensal bacteria that must be tolerated. The mechanisms that enable this tolerance are not yet fully defined. Many works have focused on active immune mechanisms involving dendritic and regulatory T cells. However, epithelial cells also make a major contribution to tolerance by influencing both innate and adaptive immunity. Therefore, the tolerogenic mechanisms concurring in the oral mucosa are intertwined. Here, we review them systematically, paying special attention to the role of oral epithelial cells

Naturally presented HLA class I–restricted epitopes from the neurotrophic factor S100-β are targets of the autoimmune response in type 1 diabetes

Type 1 diabetes (T1D) results from the destruction of pancreatic β-cells by the immune system, and CD8+ T lymphocytes are critical actors in this autoimmune response. Pancreatic islets are surrounded by a mesh of nervous cells, the peri-insular Schwann cells, which are also targeted by autoreactive T lymphocytes and express specific antigens, such as the neurotrophic factor S100-β. Previous work has shown increased proliferative responses to whole S100-β in both human T1D patients and the nonobese diabetic (NOD) mouse model. We describe for the first time naturally processed and presented epitopes (NPPEs) presented by class I human leukocyte antigen–A*02:01 (A2.1) molecules derived from S100-β. These NPPEs triggered IFN-γ responses more frequently in both newly diagnosed and long-term T1D patients compared with healthy donors. Furthermore, the same NPPEs are recognized during the autoimmune response leading to diabetes in A2.1-transgenic NOD mice as early as 4 wk of age. Interestingly, when these NPPEs are used to prevent diabetes in this animal model, an acceleration of the disease is observed together with an exacerbation in insulitis and an increase in S100-β–specific cytotoxicity in vaccinated animals. Whether these can be used in diabetes prevention needs to be carefully evaluated in animal models before use in future clinical assays.—Calviño-Sampedro, C., Gomez-Tourino, I., Cordero, O. J., Reche, P. A., Gómez-Perosanz, M., Sánchez-Trincado, J. L., Rodríguez, M. Á., Sueiro, A. M., Viñuela, J. E., Calviño, R. V. Naturally presented HLA class I–restricted epitopes from the neurotrophic factor S100-β are targets of the autoimmune response in type 1 diabetesThe authors thank Dr. Sefina Arif (King’s College London, London, United Kingdom) for critically reviewing the manuscript. This work was funded by the Ministerio de Economía y Competitividad (Grant BIO2014-53091-C3-3-R to R.V.C.). During this work, I.G.-T. was supported by a Maria Barbeito predoctoral fellowship (Xunta de Galicia, La Coruña, Spain). During this work, C.C.-S. was supported by a Deputación da Coruña grant (2012–2013 and 2016–2017)S

Metodología experimental aplicada a la Inmunología Molecular

El objetivo general del proyecto es aplicar un modelo pedagógico en el que participen los alumnos de manera activa y apliquen el método científico en base a los conocimientos que han adquirido, resolviendo y realizando un caso práctico en el laboratorio. Integra una estrategia didáctica que va a fomentar la participación activa del alumnado provocando un aprendizaje significativo, ya que el alumno tiene que resolver mediante el razonamiento un caso práctico y luego integrarlo en el laboratorio con el uso de una técnica ampliamente utilizada en Inmunología, como es la citometría de flujo.Depto. de Arquitectura de Computadores y AutomáticaFac. de InformáticaFALSEInnovasubmitte

Dihidrofolato reductasa-timidilato sintasa de Trypanosoma cruzi : caracterización del gen y de la proteína recombinante

Tesis de Granada. Facultad de Ciencia

BCEPS: A Web Server to Predict Linear B Cell Epitopes with Enhanced Immunogenicity and Cross-Reactivity

Prediction of linear B cell epitopes is of interest for the production of antigen-specific antibodies and the design of peptide-based vaccines. Here, we present BCEPS, a web server for predicting linear B cell epitopes tailored to select epitopes that are immunogenic and capable of inducing cross-reactive antibodies with native antigens. BCEPS implements various machine learning models trained on a dataset including 555 linearized conformational B cell epitopes that were mined from antibody–antigen protein structures. The best performing model, based on a support vector machine, reached an accuracy of 75.38% ± 5.02. In an independent dataset consisting of B cell epitopes retrieved from the Immune Epitope Database (IEDB), this model achieved an accuracy of 67.05%. In BCEPS, predicted epitopes can be ranked according to properties such as flexibility, accessibility and hydrophilicity, and with regard to immunogenicity, as judged by their predicted presentation by MHC II molecules. BCEPS also detects if predicted epitopes are located in ectodomains of membrane proteins and if they possess N-glycosylation sites hindering antibody recognition. Finally, we exemplified the use of BCEPS in the SARS-CoV-2 Spike protein, showing that it can identify B cell epitopes targeted by neutralizing antibodies.Comunidad de MadridUniversidad Complutense de MadridDepto. de Inmunología, Oftalmología y ORLFac. de MedicinaTRUEpu

Enhancing Regulatory T Cells to Treat Inflammatory and Autoimmune Diseases

Regulatory T cells (Tregs) control immune responses and are essential to maintain immune homeostasis and self-tolerance. Hence, it is no coincidence that autoimmune and chronic inflammatory disorders are associated with defects in Tregs. These diseases have currently no cure and are treated with palliative drugs such as immunosuppressant and immunomodulatory agents. Thereby, there is a great interest in developing medical interventions against these diseases based on enhancing Treg cell function and numbers. Here, we give an overview of Treg cell ontogeny and function, paying particular attention to mucosal Tregs. We review some notable approaches to enhance immunomodulation by Tregs with therapeutic purposes including adoptive Treg cell transfer therapy and discuss relevant clinical trials for inflammatory bowel disease. We next introduce ways to expand mucosal Tregs in vivo using microbiota and dietary products that have been the focus of clinical trials in various autoimmune and chronic-inflammatory diseases.Comunidad Autonoma de MadridDepto. de Inmunología, Oftalmología y ORLFac. de MedicinaTRUEpu

eFACS: una plataforma para la realización de practicas de laboratorio virtuales de citometría de flujo

En este proyecto hemos implementado un recurso online que permite simular el uso de un citómetro de Flujo de tres colores similar al FACScalibur. El citómetro de flujo es un instrumento esencial para la investigación básica y aplicada en biomedicina. Sin embargo, su uso requiere cierto entrenamiento y él análisis de muestras resulta costoso. Además, en universidades y hospitales no todos los departamentos disponen de un citómetro de flujo, usándose generalmente los disponibles en los centros de asistencia a la investigación. Como resultado los alumnos no tienen acceso a estos instrumentos y no tienen posibilidad de familiarizarse con las técnicas de citometría de flujo, recibiendo tan solo una información teórica sin llegar a saber hacer. En este contexto, la herramienta eFACS : • Soluciona la falta de accesibilidad y disponibilidad de citómetro de flujo para uso del estudiante • Posibilita la generación de material didáctico que permita al alumno planear y ejecutar un experimento de citometría de flujo y que aprendan haciendo. • Posibilita el entrenamiento de los usuarios en un simulador antes de enfrentarse a un citómetro de flujo real. El recurso eFACS es en conclusión un gran apoyo tanto para la docencia como para la investigación

Student-professional meetings of the degree in Human Nutrition and Dietetics. Complementary activities to the Academic Practicum

En este proyecto nos hemos centrado en la creación de un programa docente cuyo fin ha sido complementar la formación académica de los estudiantes del grado de Nutrición Humana y Dietética. Hemos acometido este proyecto con la idea de acercar a los estudiantes al desarrollo de la profesión desde el punto de vista práctico de manera interactiva. Consideramos que el programa de actividades que hemos realizado ayuda al alumno a reforzar habilidades necesarias para el desarrollo profesional, orientándoles en el emprendimiento, capacidad de comunicación eficaz, desarrollo de la creatividad y trabajo multidisciplinar.In this project we have focused on the creation of a teaching program whose purpose has been to complement the academic training of students in the Human Nutrition and Dietetics degree. We have undertaken this project with the idea of bringing students closer to the development of the profession from a practical point of view in an interactive way. We believe that the program of activities that we have carried out helps the student to reinforce the necessary skills for professional development, guiding them in entrepreneurship, effective communication skills, development of creativity and multidisciplinary work.Depto. de Inmunología, Oftalmología y ORLFac. de MedicinaFALSEsubmitte