ArticlePloS one2012
Low 2-dimensional CD4 T cell receptor affinity for myelin sets in motion delayed response kinetics.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- Induction of antigen-specific regulatory T cells by engineered extracellular vesicles.Drug delivery · 2025Article
- B Cells Influence Encephalitogenic T Cell Frequency to Myelin Oligodendrocyte Glycoprotein (MOG)38-49 during Full-length MOG Protein-Induced Demyelinating Disease.ImmunoHorizons · 2024Article
- Chronic infection control relies on T cells with lower foreign antigen binding strength generated by N-nucleotide diversity.PLoS biology · 2024Article
- Integrin α3 promotes TScience immunology · 2023Article
- What's the Catch? The Significance of Catch Bonds in T Cell Activation.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- Visualizing the activation of encephalitogenic T cells in the ileal lamina propria by in vivo two-photon imaging.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Cholinergic control of Th17 cell pathogenicity in experimental autoimmune encephalomyelitis.Cell death and differentiation · 2023Article
- Antigen-specific depletion of CD4Science immunology · 2022Article
- Genetic Bias, Diversity Indices, Physiochemical Properties and CDR3 Motifs Divide Auto-Reactive from Allo-Reactive T-Cell Repertoires.International journal of molecular sciences · 2021Article
- miR-21 sustains CD28 signalling and low-affinity T-cell responses at the expense of self-tolerance.Clinical & translational immunology · 2021Article
- Biomechanics of T Cell Dysfunctions in Chronic Diseases.Frontiers in immunology · 2021Review
- Relationship of 2D Affinity to T Cell Functional Outcomes.International journal of molecular sciences · 2020Review
- A Hybrid Insulin Epitope Maintains High 2D Affinity for Diabetogenic T Cells in the Periphery.Diabetes · 2020Article
- Regulation of T Helper Cell Fate by TCR Signal Strength.Frontiers in immunology · 2020Review
- CD4 T Cell Affinity Diversity Is Equally Maintained during Acute and Chronic Infection.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- 2D Kinetic Analysis of TCR and CD8 Coreceptor for LCMV GP33 Epitopes.Frontiers in immunology · 2018Article
- NFM Cross-Reactivity to MOG Does Not Expand a Critical Threshold Level of High-Affinity T Cells Necessary for Onset of Demyelinating Disease.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- A role for cathepsin Z in neuroinflammation provides mechanistic support for an epigenetic risk factor in multiple sclerosis.Journal of neuroinflammation · 2017Article
- Understanding Autoimmune Diabetes through the Prism of the Tri-Molecular Complex.Frontiers in endocrinology · 2017Review
- Low-affinity CD4+ T cells are major responders in the primary immune response.Nature communications · 2016Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
T cells recognizing self-peptides that mediate autoimmune disease and those that are responsible for efficacious immunity against pathogens may differ in affinity for antigen due to central and peripheral tolerance mechanisms. Here we utilize prototypical self-reactive (myelin) and viral-specific (LCMV) T cells from T cell receptor (TCR) transgenic mice (2D2 and SMARTA, respectively) to explore affinity differences. The T cells responsive to virus possessed >10,000 fold higher 2D affinity as compared to the self-reactive T cells. Despite their dramatically lower affinity for their cognate ligand, 2D2 T cells respond with complete, albeit delayed, activation (proliferation and cytokine production). SMARTA activation occurs rapidly, achieving peak phosphorylation of p38 (1 minute), Erk (30 minutes), and Jun (3 hours) as well as CD69 and CD25 upregulation (3 and 6 hours, respectively), with a corresponding early initiation of proliferation. 2D2 stimulation with MOG results in altered signaling--no phospho-Erk or phospho-p38 accumulation, significantly delayed activation kinetics of Jun (12 hours), and delayed but sustained SHP-1 activity--as well as delayed CD69 and CD25 expression (12-24 hours), and slow initiation of proliferation. This delay was not intrinsic to the 2D2 T cells, as a more potent antigen with >100-fold increased 2D affinity restored rapid response kinetics in line with those identified for the viral antigen. Taken together, these data demonstrate that time can offset low TCR affinity to attain full activation and suggest a mechanism by which low affinity T cells participate in autoimmune disease.
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