ArticleProceedings of the National Academy of Sciences of the United States of America1997
Characterization of the major histocompatibility complex class II binding site on LAG-3 protein.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 162 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
162 citing papers in PubMed, 301 citations in OpenAlex.
- LAG3 checkpoint function and its mechanism of action in therapeutic targeting.Nature reviews. Immunology · 2026Review
- The Cardio-Onco-Immune Axis: immunopathological mechanisms in the cardiac microenvironment of checkpoint inhibitor-induced myocarditis.Acta pharmacologica Sinica · 2026Review
- Viral load-driven systemic immune exhaustion is an enabler of antibody breadth in HIV infection.bioRxiv : the preprint server for biology · 2026Article
- Insight of immune checkpoint blockades in melanoma: mechanism and clinical translation.Molecular cancer · 2026Review
- Myeloid Malignancies Beyond the Cell: Targeting the Tumour Microenvironment with Next-Generation Immunotherapies.Cancers · 2026Review
- Review
- Article
- Walking the tightrope: Balancing immune checkpoints and their inhibitors in host defence against bacterial infections.Journal of applied biomedicine · 2026Review
- Immune checkpoint TIM-3 in tumor immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- Revitalizing T cells: breakthroughs and challenges in overcoming T cell exhaustion.Signal transduction and targeted therapy · 2026Review
- A Peptide Inhibitor of Lymphocyte Activation Gene-3 Interaction with Fibrinogen-like Protein 1 Synergizes with Programmed Death-Ligand 1 Blockade to Restore T Cell Activity and Inhibit Tumor Growth.Biomaterials research · 2026Article
- Elevated Levels of sLAG-3 as a Possible Biomarker in Graves' Disease With and Without Thyroid Eye Disease: A Prospective Observational Case-Control Study.Medicina (Kaunas, Lithuania) · 2025Observational
- Emerging new immune checkpoint inhibitors in solid tumor immunotherapy.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Phenotypic and targeted drug discovery in immune therapeutics: challenges, opportunities, and future directions.RSC advances · 2025Review
- Design of Ig-like binders targeting α-synuclein fibril for mitigating its pathological activities.Nature communications · 2025Article
- Rationale of using immune checkpoint inhibitors (ICIs) and anti-angiogenic agents in cancer treatment from a molecular perspective.Clinical and experimental medicine · 2025Review
- Exploring new frontiers in LAG-3 biology and therapeutics.Trends in pharmacological sciences · 2025Review
- LAG3 regulates antibody responses in a murine model of kidney transplantation.The Journal of clinical investigation · 2025Article
- Unravelling T cell exhaustion through co-inhibitory receptors and its transformative role in cancer immunotherapy.Clinical and translational medicine · 2025Review
- LAG Time in the Era of Immunotherapy-New Molecular Insights Into the Immunosuppression Mechanism of Lymphocyte Activation Gene-3.Immunological reviews · 2025Review
102 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The lymphocyte activation gene-3 (LAG-3), selectively transcribed in human activated T and NK cells, encodes a ligand for major histocompatibility complex (MHC) class II molecules. Like CD4, LAG-3 ectodomain is composed of four Ig-like domains (D1-D4). Nothing is known about the LAG-3 regions or residues required to form a stable MHC class II binding site. In contrast to CD4, soluble LAG-3 molecules stably interact with MHC class II molecules expressed on the cell surface. In addition, the first two N-terminal domains of soluble LAG-3 (D1 and D2) molecules, alone, are capable of binding MHC class II. From a LAG-3 model structure, we designed mutants and tested their ability to bind MHC class II molecules in an intercellular adhesion assay. We found residues on the membrane-distal, CDR1-2-containing top face of D1 that are essential for either binding or repulsing MHC class II proteins. Most of these residues are clustered at the base of a large extra-loop structure that is a hallmark of the LAG-3 D1 Ig-like domain. In addition, as for CD4, oligomerization of LAG-3 on the cell surface may be required to form a stable MHC binding site because mutation of three residues in the ABED beta-strands containing side of D1 results in a dominant negative effect (i.e., binding inhibition of coexpressed wild-type LAG-3).
Indexed as
Identifiers
What OpenQuestion holds
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.