A5049853066- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- SARS-CoV-2 and COVID-19 Research
- Monoclonal and Polyclonal Antibodies Research
- COVID-19 Clinical Research Studies
- Diabetes and associated disorders
- Receptor Mechanisms and Signaling
- SARS-CoV-2 detection and testing
- Cytomegalovirus and herpesvirus research
- vaccines and immunoinformatics approaches
- Glycosylation and Glycoproteins Research
- Comparative International Legal Studies
- Glioma Diagnosis and Treatment
- Tuberculosis Research and Epidemiology
- Virus-based gene therapy research
- Immune cells in cancer
- Single-cell and spatial transcriptomics
- Advanced biosensing and bioanalysis techniques
- Ubiquitin and proteasome pathways
- Synthesis and Biological Evaluation
- HIV Research and Treatment
- Cell Adhesion Molecules Research
- RNA Interference and Gene Delivery
Consejo Superior de Investigaciones Científicas
2013-2024
Centro de Biología Molecular Severo Ochoa
2010-2024
Universidad Autónoma de Madrid
2013-2024
Harvard University
2004-2022
Wilhelmina Children's Hospital
2016-2019
University Medical Center Utrecht
2016-2019
Max Planck Institute of Immunobiology and Epigenetics
2008
University of Freiburg
2008
Joslin Diabetes Center
2004-2007
Brigham and Women's Hospital
2004-2007
A long-standing paradox in the study of T cell antigen recognition is that high specificity–low affinity receptor (TCR)–major histocompatibility complex peptide (MHCp) interaction. The existence multivalent TCRs could resolve this because they can simultaneously improve avidity observed for monovalent interactions and allow cooperative effects. We have studied stoichiometry TCR by Blue Native–polyacrylamide gel electrophoresis found exists as a mixture (αβγεδεζζ) complexes with two or more...
For CD8(+) T cells, a relatively short antigen pulse seems sufficient for antigen-presenting cells to drive clonal expansion and differentiation. It is unknown whether the requirement similarly ephemeral CD4(+) cells. To study dependence of cell response on persistence in quantitatively temporally controlled manner vivo, we engineered mouse line expressing major histocompatibility complex class II-restricted epitope dendritic under control tetracycline-inducible promoter. Experiments...
It has been reported that the differentiation of CD4+CD25+ regulatory T cells (T reg cells) can be induced by agonist peptide/major histocompatibility complex ligands in thymus. Exploiting a transgenic mouse line wherein expression particular cell epitope controlled temporally and quantitatively, we found diversion differentiating thymocytes into FoxP3 pathway this ligand was essentially nonexistent. However, were much less sensitive than their CD4+CD25- companions, two to three orders...
Cell-mediated immune responses are essential for protection against many intracellular pathogens. For Mycobacterium tuberculosis (MTB), requires the activity of T cells that recognize antigens presented in context both major histocompatibility complex (MHC) class II and I molecules. Since MHC presentation generally antigen to be localized cytoplasmic compartment antigen-presenting cells, it remains unclear how pathogens reside primarily within endocytic vesicles infected macrophages, such as...
Misfolded membrane proteins are rapidly degraded, often shortly after their synthesis and insertion in the endoplasmic reticulum (ER), but exact location mechanisms of breakdown remain unclear. We have exploited requirement MHC class I molecules for peptide to achieve correct conformation: can be withheld by introducing a null mutation MHC-encoded transporter, TAP. By withholding TAP-dependent peptides, vast majority newly synthesized fails leave is degraded. used mice transgenic HLA-B27 on...
Activation of dendritic cells (DCs) enhances their ability to prime naïve T cells. How activation renders them immunogenic rather than tolerogenic is unclear. Here, we show, using temporally regulated expression a transgene-encoded neoself antigen in DCs, that either prolonged presentation or DC could elicit full expansion, effector cytokine production, and memory-cell differentiation. Microarray analysis gene showed all changes linked through CD40 be reproduced by persistent delivery,...
Article17 February 2021Open Access Transparent process Flow cytometry multiplexed method for the detection of neutralizing human antibodies to native SARS-CoV-2 spike protein Lydia Horndler Centro de Biología Molecular Severo Ochoa, Consejo Superior Investigaciones Científicas (CSIC), Universidad Autónoma Madrid, Spain Search more papers by this author Pilar Delgado David Abia Bioinformatics Facility, Ivaylo Balabanov Pedro Martínez-Fleta Immunology Department, Hospital Universitario La...
Background COVID‐19 can generate a broad spectrum of severity and symptoms. Many studies analysed the determinants but not among some types More importantly, very few patients highly exposed to virus that nonetheless remain uninfected. Methods We serum levels ACE2, Angiotensin II anti-Spike antibodies in 2 different cohorts at high risk viral exposure, uninfected subjects, either health care workers or persons cohabiting with infected close relatives seropositive tested ability sera these...
The human cell line T2 has been reported to be class I assembly deficient, and accordingly expresses reduced amounts of HLA-A2 no HLA-B5 at the surface. By immunoblotting we observe steady-state heavy chain levels near normal when compared with identical alleles wild-type T1. In pulse chase experiments, formation beta 2-microglobulin complexes is observed for both HLA-B5. Culture temperatures (26 or 20 degrees C) does not increase amount molecules transported, unlike what assembly-deficient...
T cells form immunological synapses with professional antigen-presenting (APCs) resulting in cell activation and the acquisition of peptide antigen-MHC (pMHC) complexes from plasma membrane APC. They thus become APCs themselves. We investigate functional outcome T-T antigen presentation by CD4 find that (Tpres) predominantly differentiate into regulatory (Treg), whereas have been stimulated Tpres Th17 pro-inflammatory cells. Using mice deficient pMHC uptake cells, we show is important for...
T cell antigen receptor (TCR) triggering determines the fate of immature thymocytes. The affinity TCR for its endogenous peptide/MHC ligands serves as a signal positive or negative selection through mechanisms that are still little understood. We have used conformation-specific antibody to demonstrate recognition lead induces conformational change in situ. In contrast, this is elicited only small percentage thymocytes during selection. Using TUNEL assay, we strongly linked activation...
Antigenic T cell stimulation requires interaction between the TCR of and cognate peptide-MHC molecules presented by APC. Although studies with TCR-specific Abs soluble ligands have shown that needs to be crosslinked two or more induce stimulation, it is not understood how several MHC loaded antigenic peptide can produce crosslinking under physiological conditions. We show at molecular level large clusters are formed surface murine professional nonprofessional APCs upon virus infection these...
Conventional and regulatory T cells develop in the thymus where they are exposed to samples of self-peptide MHC (pMHC) ligands. This probabilistic process selects for within a range responsiveness that allows detection foreign antigen without excessive responses self. Regulatory thought lie at higher end spectrum acceptable self-reactivity play crucial role control autoimmunity tolerance innocuous antigens. While many studies have elucidated key elements influencing lineage commitment, we...
Article11 June 2020Open Access Source DataTransparent process CCR5 deficiency impairs CD4+ T-cell memory responses and antigenic sensitivity through increased ceramide synthesis Ana Martín-Leal Department of Immunology Oncology, Centro Nacional de Biotecnología (CNB/CSIC), Madrid, Spain Search for more papers by this author Raquel Blanco Josefina Casas Biological Chemistry, Institute Advanced Chemistry Catalonia (IQAC-CSIC), Barcelona, CIBER Liver Digestive Diseases (CIBER-EDH), Instituto...
The rapid development of vaccines to prevent COVID-19 has raised the need compare capacity different in terms developing a protective humoral response. Previous studies have shown inconsistent results this area, highlighting importance further research evaluate efficacy vaccines. This study utilized highly sensitive and reliable flow cytometry method measure titers IgG1 isotype antibodies blood healthy volunteers after receiving one or two doses various administered Spain. was also used...
Mice harboring a deletion of the gene encoding transporter associated with antigen presentation-1 (TAP1) are impaired in providing major histocompatibility complex (MHC) class I molecules peptides cytosolic origin and lack stable MHC cell surface expression. They consequently have strongly reduced number CD8+ T cells. To examine whether selection cells is dependent on TAP-dependent peptides, we partially restored expression TAP1-deficient mice by introduction human beta 2-microglobulin. We...
Major histocompatibility complex (MHC) class I and II molecules are loaded with peptides in distinct subcellular compartments. The transporter associated antigen processing (TAP) is responsible for delivering derived from cytosolic proteins to the endoplasmic reticulum, where they bind molecules, while invariant chain (Ii) directs endosomal compartments, originating mostly exogenous sources. Mice carrying null mutations of TAP1 or Ii genes (TAP10) Ii0, respectively) have been useful tools...
Significance The ability of the T cell receptor (TCR) to convey signals different intensity is essential for generation a diverse, protecting, and self-tolerant repertoire. We provide evidence that pre-TCR signaling during first stage differentiation, thought only check in-frame rearrangement TCRβ gene segments, determines degree diversity in intensity–dependent manner controls TCR repertoire available subsequent thymic positive negative selection. Pre-TCR regulated by transmembrane region...