ArticleProceedings of the National Academy of Sciences of the United States of America2016
Functional evidence for TCR-intrinsic specificity for MHCII.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 28 citations in OpenAlex.
- Article
- The CD4 transmembrane GGXXG and juxtamembrane (C/F)CV+C motifs mediate pMHCII-specific signaling independently of CD4-LCK interactions.bioRxiv : the preprint server for biology · 2023Article
- Sphingomyelin-derived nanovesicles for the delivery of the IDO1 inhibitor epacadostat enhance metastatic and post-surgical melanoma immunotherapy.Nature communications · 2023Article
- The TCR Cα Domain Regulates Responses to Self-pMHC Class II.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- The Early Peritoneal Cavity Immune Response toMicroorganisms · 2022Article
- Article
- A biomimetic five-module chimeric antigen receptor (Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- CD4 Inhibits Helper T Cell Activation at Lower Affinity Threshold for Full-Length T Cell Receptors Than Single Chain Signaling Constructs.Frontiers in immunology · 2020Article
- Designs of Antigen Structure and Composition for Improved Protein-Based Vaccine Efficacy.Frontiers in immunology · 2020Review
- Coreceptors and TCR Signaling - the Strong and the Weak of It.Frontiers in cell and developmental biology · 2020Review
- Inherent reactivity of unselected TCR repertoires to peptide-MHC molecules.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Tumor progression mechanisms: Insights from the central immune regulation of tissue homeostasis.Oncology letters · 2019Review
- Germline-Encoded TCR-MHC Contacts Promote TCR V Gene Bias in Umbilical Cord Blood T Cell Repertoire.Frontiers in immunology · 2019Article
- An integrated strategy for identifying new targets and inferring the mechanism of action: taking rhein as an example.BMC bioinformatics · 2018Article
- Understanding the drivers of MHC restriction of T cell receptors.Nature reviews. Immunology · 2018Review
- Reciprocal TCR-CD3 and CD4 Engagement of a Nucleating pMHCII Stabilizes a Functional Receptor Macrocomplex.Cell reports · 2018Article
- Genetic variation in MHC proteins is associated with T cell receptor expression biases.Nature genetics · 2016Article
- The CD4 and CD3δε Cytosolic Juxtamembrane Regions Are Proximal within a Compact TCR-CD3-pMHC-CD4 Macrocomplex.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Revealing the TCR bias for MHC molecules.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
Corrections and comments
- Commented on by
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
How T cells become restricted to binding antigenic peptides within class I or class II major histocompatibility complex molecules (pMHCI or pMHCII, respectively) via clonotypic T-cell receptors (TCRs) remains debated. During development, if TCR-pMHC interactions exceed an affinity threshold, a signal is generated that positively selects the thymocyte to become a mature CD4(+) or CD8(+) T cell that can recognize foreign peptides within MHCII or MHCI, respectively. But whether TCRs possess an intrinsic, subthreshold specificity for MHC that facilitates sampling of the peptides within MHC during positive selection or T-cell activation is undefined. Here we asked if increasing the frequency of lymphocyte-specific protein tyrosine kinase (Lck)-associated CD4 molecules in T-cell hybridomas would allow for the detection of subthreshold TCR-MHC interactions. The reactivity of 10 distinct TCRs was assessed in response to selecting and nonselecting MHCII bearing cognate, null, or "shaved" peptides with alanine substitutions at known TCR contact residues: Three of the TCRs were selected on MHCII and have defined peptide specificity, two were selected on MHCI and have a known pMHC specificity, and five were generated in vitro without defined selecting or cognate pMHC. Our central finding is that IL-2 was made when each TCR interacted with selecting or nonselecting MHCII presenting shaved peptides. These responses were abrogated by anti-CD4 antibodies and mutagenesis of CD4. They were also inhibited by anti-MHC antibodies that block TCR-MHCII interactions. We interpret these data as functional evidence for TCR-intrinsic specificity for MHCII.
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.