A5090367243- HIV Research and Treatment
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- vaccines and immunoinformatics approaches
- HIV/AIDS drug development and treatment
- Cytomegalovirus and herpesvirus research
- HIV/AIDS Research and Interventions
- Immunotherapy and Immune Responses
- Hepatitis B Virus Studies
- Hepatitis C virus research
- Viral-associated cancers and disorders
- Herpesvirus Infections and Treatments
- Gut microbiota and health
- Immunodeficiency and Autoimmune Disorders
- HIV-related health complications and treatments
- SARS-CoV-2 and COVID-19 Research
- Reproductive System and Pregnancy
- Monoclonal and Polyclonal Antibodies Research
- Liver Disease Diagnosis and Treatment
- COVID-19 Clinical Research Studies
- RNA Interference and Gene Delivery
- Drug-Induced Adverse Reactions
- Clostridium difficile and Clostridium perfringens research
- Influenza Virus Research Studies
- Immune responses and vaccinations
Instituto de Salud Carlos III
2022-2025
IrsiCaixa
2016-2025
Universitat de Vic - Universitat Central de Catalunya
2016-2025
Centro de Investigación Biomédica en Red
2021-2025
Institució Catalana de Recerca i Estudis Avançats
2015-2024
Universitat Autònoma de Barcelona
2009-2023
Hospital Universitari Germans Trias i Pujol
2013-2023
Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol
2011-2023
Institut Català de Ciències del Clima
2019-2021
Red de Investigación en Sida
2012-2020
Abstract Background Class I major histocompatibility complex (MHC) molecules bind, and present to T cells, short peptides derived from intracellular processing of proteins. The peptide repertoire a specific molecule is large extent determined by the molecular structure accommodating so-called main anchor positions presented peptide. These receptors are extremely polymorphic, much polymorphism influences peptide-binding repertoire. However, despite this polymorphism, class can be clustered...
Cellular immune responses play a critical role in the control of human immunodeficiency virus type 1 (HIV-1); however, breadth these at single-epitope level has not been comprehensively assessed. We therefore screened peripheral blood mononuclear cells (PBMC) from 57 individuals different stages HIV-1 infection for virus-specific T-cell using matrix 504 overlapping peptides spanning all expressed proteins gamma interferon-enzyme-linked immunospot (Elispot) assay. HIV-1-specific were...
The immune response to HIV-1 in patients who carry human histocompatibility leukocyte antigen (HLA)-B27 is characterized by an immunodominant epitope p24 gag (amino acids 263–272, KRWIILGLNK). Substitution of lysine (K) or glycine (G) for arginine (R) at residue 264 (R264K and R264G) results epitopes that bind HLA-B27 poorly. We have detected a R264K mutation four carrying HLA-B27. In three these the occurred late, coinciding with disease progression. another it within 1 yr infection was...
Mutational escape by human immunodeficiency virus (HIV) from cytotoxic T-lymphocyte (CTL) recognition is a major challenge for vaccine design. However, recent studies suggest that CTL may carry sufficient cost to viral replicative capacity facilitate subsequent immune control of now attenuated virus. In order examine how limitations can be imposed on escape, the epitope TSTLQEQIGW (TW10 [Gag residues 240 249]), presented two HLA alleles associated with effective HIV, HLA-B*57 and -B*5801,...
Decline of peak viremia during acute HIV-1 infection occurs before the development vigorous adaptive immunity, and level decline correlates inversely with rate AIDS progression, implicating a potential role for innate immune response in determining disease outcome. The combined expression an activating natural killer (NK) cell receptor, immunoglobulin-like receptor (KIR) 3DS1, its presumed ligand, human leukocyte antigen (HLA)–B Bw4-80I, has been associated epidemiological studies slow...
The human virome plays important roles in health and immunity. However, current methods for detecting viral infections antiviral responses have limited throughput coverage. Here, we present VirScan, a high-throughput method to comprehensively analyze antibodies using immunoprecipitation massively parallel DNA sequencing of bacteriophage library displaying proteome-wide peptides from all viruses. We assayed over 10(8) antibody-peptide interactions 569 humans across four continents, nearly...
Immune responses induced during the early stages of chronic viral infections are thought to influence disease outcome. Using HIV as a model, we examined virus-specific cytotoxic T lymphocytes (CTLs), helper cells, and genetic diversity in relation duration infection subsequent response antiviral therapy. Individuals with acute HIV-1 treated before seroconversion had weaker CTL directed at fewer epitopes than persons who were after seroconversion. However, treatment-induced control viremia...
Deep sequencing technologies have the potential to transform study of highly variable viral pathogens by providing a rapid and cost-effective approach sensitively characterize rapidly evolving quasispecies. Here, we report on high-throughput whole HIV-1 genome deep platform that combines 454 pyrosequencing with novel assembly variant detection algorithms. In one subject combined these genetic data detailed immunological analyses comprehensively evaluate evolution immune escape during acute...
ABSTRACT The sequence diversity of human immunodeficiency virus type 1 (HIV-1) represents a major obstacle to the development an effective vaccine, yet forces impacting evolution this pathogen remain unclear. To address issue we assessed relationship between genome-wide viral and adaptive CD8 + T-cell responses in four clade B virus-infected patients studied longitudinally for as long 5 years after acute infection. Of 98 amino acid mutations identified nonenvelope antigens, 53% were...
ABSTRACT Human leukocyte antigen (HLA)-B27-positive subjects are uncommon in their ability to control infection with human immunodeficiency virus type 1 (HIV-1). However, late viral escape from a narrowly directed immunodominant Gag-specific CD8 + T-lymphocyte (CTL) response has been linked AIDS progression these individuals. Identifying the mechanism of immune-mediated may provide critical insights into HIV-1 vaccine development. Here, we illustrate that CTL mutation R 264 K...
Human immunodeficiency virus type 1 (HIV-1) elite controllers (EC) maintain viremia below the limit of commercial assay detection (<50 RNA copies/ml) in absence antiviral therapy, but mechanisms control remain unclear. HLA-B57 and closely related allele B*5801 are particularly associated with enhanced recognize same Gag(240-249) TW10 epitope. The typical escape mutation (T242N) within this epitope diminishes viral replication capacity chronically infected persons; however, little is known...
The generation of humanized BLT mice by the cotransplantation human fetal thymus and liver tissues CD34(+) cells into nonobese diabetic/severe combined immunodeficiency allows for long-term reconstitution a functional immune system, with T cells, B dendritic monocytes/macrophages repopulating mouse tissues. Here, we show that sustained high-level disseminated virus (HIV) infection, resulting in CD4(+) T-cell depletion generalized activation. Following HIV-specific humoral responses were...
The transcription factor TOX is not exclusively linked to T cell exhaustion (see related Focus by Utzschneider and Kallies).
Abstract To investigate how T cells are involved in hypersensitivity reactions to drugs that become immunogenic after metabolization, e.g., sulfonamides and antiepileptics, we analyzed vitro the drug-induced activation of CD4+ CD8+ cell subsets, cytokine secretion, TCR V beta distribution, proliferation from four drug-allergic individuals. In addition, parameters CD25 HLA-DR were vivo on five patients with acute drug allergies, some them anticonvulsant syndrome hepatitis. Our results show...
Mutations within cytotoxic T lymphocyte (CTL) epitopes impair cell recognition, but escape mutations arising in flanking regions that alter antigen processing have not been defined natural human infections. In histocompatibility leukocyte (HLA)-B57+ HIV-infected persons, immune selection pressure leads to a mutation from alanine proline at Gag residue 146 immediately preceding the NH2 terminus of dominant HLA-B57–restricted epitope, ISPRTLNAW. Although N-extended wild-type or mutant peptides...
Conflicting data on the role of total virus- and protein-specific cytotoxic-T-lymphocyte (CTL) responses in control human immunodeficiency virus (HIV) disease progression exist. We present generated from a Peruvian cohort untreated, clade B-infected subjects, demonstrating that proportion Gag-specific, particular p24-reactive, CTL among virus-specific activity is associated with individuals' CD4 counts viral loads. Analyses second United States confirm these findings point towards dominant...