ArticleProceedings of the National Academy of Sciences of the United States of America2011
Structural and functional characterization of a single-chain peptide-MHC molecule that modulates both naive and activated CD8+ T cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed.
- Multiscale conformational sampling of multidomain fusion proteins by a physics informed diffusion model.bioRxiv : the preprint server for biology · 2026Article
- Recruiting ESCRT to single-chain heterotrimer peptide MHCI releases antigen-presenting vesicles that stimulate T cells selectively.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Current and Emerging Assays for Measuring Human T-Cell Responses Against Beta-Cell Antigens in Type 1 Diabetes.Biomolecules · 2025Review
- Evolving understanding of autoimmune mechanisms and new therapeutic strategies of autoimmune disorders.Signal transduction and targeted therapy · 2024Review
- Methodology of stable peptide based on propargylated sulfonium.Biochemistry and biophysics reports · 2023Article
- Article
- Understanding the Targeting Mechanisms of Multi-Specific Biologics in Immunotherapy with Multiscale Modeling.iScience · 2020Article
- Structural Insights into N-terminal IgV Domain of BTNL2, a T Cell Inhibitory Molecule, Suggests a Non-canonical Binding Interface for Its Putative Receptors.Journal of molecular biology · 2020Article
- MHC-restricted Ag85B-specific CD8European journal of immunology · 2019Article
- General principles of binding between cell surface receptors and multi-specific ligands: A computational study.PLoS computational biology · 2017Article
- Characterization of Diabetogenic CD8+ T Cells: IMMUNE THERAPY WITH METABOLIC BLOCKADE.The Journal of biological chemistry · 2016Article
- Beta cell antigens in type 1 diabetes: triggers in pathogenesis and therapeutic targets.F1000Research · 2016Review
- Lymphocyte repertoire selection and intracellular self/non-self-discrimination: historical overview.Immunology and cell biology · 2015Review
- DEC-205-mediated antigen targeting to steady-state dendritic cells induces deletion of diabetogenic CD8⁺ T cells independently of PD-1 and PD-L1.International immunology · 2013Article
- Amino-terminal extended peptide single-chain trimers are potent synthetic agonists for memory human CD8+ T cells.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- The use of peptide-major-histocompatibility-complex multimers in type 1 diabetes mellitus.Journal of diabetes science and technology · 2012Review
- Making the most of major histocompatibility complex molecule multimers: applications in type 1 diabetes.Clinical & developmental immunology · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
Peptide-MHC (pMHC) multimers, in addition to being tools for tracking and quantifying antigen-specific T cells, can mediate downstream signaling after T-cell receptor engagement. In the absence of costimulation, this can lead to anergy or apoptosis of cognate T cells, a property that could be exploited in the setting of autoimmune disease. Most studies with class I pMHC multimers used noncovalently linked peptides, which can allow unwanted CD8(+) T-cell activation as a result of peptide transfer to cellular MHC molecules. To circumvent this problem, and given the role of self-reactive CD8(+) T cells in the development of type 1 diabetes, we designed a single-chain pMHC complex (scK(d).IGRP) by using the class I MHC molecule H-2K(d) and a covalently linked peptide derived from islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP(206-214)), a well established autoantigen in NOD mice. X-ray diffraction studies revealed that the peptide is presented in the groove of the MHC molecule in canonical fashion, and it was also demonstrated that scK(d).IGRP tetramers bound specifically to cognate CD8(+) T cells. Tetramer binding induced death of naive T cells and in vitro- and in vivo-differentiated cytotoxic T lymphocytes, and tetramer-treated cytotoxic T lymphocytes showed a diminished IFN-γ response to antigen stimulation. Tetramer accessibility to disease-relevant T cells in vivo was also demonstrated. Our study suggests the potential of single-chain pMHC tetramers as possible therapeutic agents in autoimmune disease. Their ability to affect the fate of naive and activated CD8(+) T cells makes them a potential intervention strategy in early and late stages of disease.
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.