ArticleThe Journal of experimental medicine2000
Visualization of myelin basic protein (MBP) T cell epitopes in multiple sclerosis lesions using a monoclonal antibody specific for the human histocompatibility leukocyte antigen (HLA)-DR2-MBP 85-99 complex.
Article in The Journal of experimental medicine, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 73 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
73 citing papers in PubMed, 196 citations in OpenAlex.
- Dynamics of Myelin-Specific T-Cell Repertoires Mirror Disease Activity and Central Nervous System Trafficking in Multiple Sclerosis.International journal of molecular sciences · 2026Article
- HLA-DRB1*15:01 drives sex- and age-dependent microglial activation and neuroimmune signaling.bioRxiv : the preprint server for biology · 2026Article
- HLA polymorphism in neuroimmune diseases: linking antigen presentation to neuroinflammatory programs.Frontiers in immunology · 2026Review
- HLA-DRB1*15:01 drives sex- and age-dependent microglial immune phenotypes and neuroimmune signaling.Frontiers in immunology · 2026Article
- Myeloid ZNRF1 suppresses autoimmune demyelination and neuroinflammation by regulating MHC-II-mediated T cell activation.Journal of neuroinflammation · 2025Article
- Antigen-specific modulation of chronic experimental autoimmune encephalomyelitis in humanized mice by TCR-like antibody targeting autoreactive T-cell epitope.Life science alliance · 2025Article
- Review
- Macrophages and HLA-Class II Alleles in Multiple Sclerosis: Insights in Therapeutic Dynamics.International journal of molecular sciences · 2024Review
- Myelin Basic Protein in Oligodendrocyte-Derived Extracellular Vesicles as a Diagnostic and Prognostic Biomarker in Multiple Sclerosis: A Pilot Study.International journal of molecular sciences · 2023Article
- The immunology of multiple sclerosis.Nature reviews. Immunology · 2022Review
- TCR-like antibodies targeting autoantigen-mhc complexes: a mini-review.Frontiers in immunology · 2022Review
- A high-affinity human TCR-like antibody detects celiac disease gluten peptide-MHC complexes and inhibits T cell activation.Science immunology · 2021Article
- Aberrant DNA methylation profile exacerbates inflammation and neurodegeneration in multiple sclerosis patients.Journal of neuroinflammation · 2020Review
- Single-Domain Antibody-Based TCR-Like CAR-T: A Potential Cancer Therapy.Journal of immunology research · 2020Review
- Targeting the MHC Ligandome by Use of TCR-Like Antibodies.Antibodies (Basel, Switzerland) · 2019Review
- Design and molecular dynamic simulation of a new double-epitope tolerogenic protein as a potential vaccine for multiple sclerosis disease.Research in pharmaceutical sciences · 2019Article
- Structure-based selection of human metabolite binding P4 pocket of DRB1*15:01 and DRB1*15:03, with implications for multiple sclerosis.Genes and immunity · 2019Article
- An Overview of the Intrinsic Role of Citrullination in Autoimmune Disorders.Journal of immunology research · 2019Review
- Opportunities and Challenges for Antibodies against Intracellular Antigens.Theranostics · 2019Review
- Anti-Mycobacterial Antibodies in Paired Cerebrospinal Fluid and Serum Samples from Japanese Patients with Multiple Sclerosis or Neuromyelitis Optica Spectrum Disorder.Journal of clinical medicine · 2018Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedCanella B [corrected to Cannella B]
Authors and funding
11 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Susceptibility to multiple sclerosis (MS) is associated with the human histocompatibility leukocyte antigen (HLA)-DR2 haplotype, suggesting that major histocompatibility complex class II-restricted presentation of central nervous system-derived antigens is important in the disease process. Antibodies specific for defined HLA-DR2-peptide complexes may therefore be valuable tools for studying antigen presentation in MS. We have used phage display technology to select HLA-DR2-peptide-specific antibodies from HLA-DR2-transgenic mice immunized with HLA-DR2 molecules complexed with an immunodominant myelin basic protein (MBP) peptide (residues 85-99). Detailed characterization of one clone (MK16) demonstrated that both DR2 and the MBP peptide were required for recognition. Furthermore, MK16 labeled intra- and extracellular HLA-DR2-MBP peptide complexes when antigen-presenting cells (APCs) were pulsed with recombinant MBP. In addition, MK16 inhibited interleukin 2 secretion by two transfectants that expressed human MBP-specific T cell receptors. Analysis of the structural requirement for MK16 binding demonstrated that the two major HLA-DR2 anchor residues of MBP 85-99 and the COOH-terminal part of the peptide, in particular residues Val-96, Pro-98, and Arg-99, were important for binding. Based on these results, the antibody was used to determine if the HLA-DR2-MBP peptide complex is presented in MS lesions. The antibody stained APCs in MS lesions, in particular microglia/macrophages but also in some cases hypertrophic astrocytes. Staining of APCs was only observed in MS cases with the HLA-DR2 haplotype but not in cases that carried other haplotypes. These results demonstrate that HLA-DR2 molecules in MS lesions present a myelin-derived self-peptide and suggest that microglia/macrophages rather than astrocytes are the predominant APCs in these lesions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.