Development of MHC Class I Blocking Peptides to Target Metabolic Dysfunction-Associated Steatohepatitis CD8+ T Cell Activation
Adams, V.; Sarma, S.; Hall, C. K.; Kennedy, A.
Show abstract
MHC class I molecules play a crucial role in the immune system by presenting peptides derived from intracellular proteins to cytotoxic T lymphocytes (CTLs). This process is essential for immune surveillance and eliminating infected or malignant cells. In some diseases, the immune system fails to recognize and eliminate abnormal cells, leading to disease progression. Under conditions of metabolic dysfunction-associated steatohepatitis (MASH), subsets of CD8+ T cells have been identified as pathogenic, leading to inflammation and fibrosis. Therefore, explicitly targeting factors responsible for T cell activation may be necessary to prevent the onset of MASH and future complications such as cirrhosis or hepatocellular carcinoma. We have identified a specific MHC class I antigen that activates hepatic and splenic CD8+ T cells isolated from MASH mice. To specifically target the antigen, we developed two MHC H2-Kb blocking peptides, MHCP3 and MHCP5, that competitively inhibit the Ncf2 peptide from binding to H2-Kb and reduce activation and proliferation of CD8+ T cells. By inhibiting the recognition of specific antigens, these blocking peptides may prevent the activation of CD8+ T cells and progression of MASH.
Matching journals
The top 11 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Feature Selection Enhances Peptide Binding Predictions for TCR-Specific Interactions 94%
- CLICK-chemoproteomics and molecular dynamics simulation reveals pregnenolone targets and their binding conformations in Th2 cells 93%
- Large-scale template-based structural modeling of T-cell receptors with known antigen specificity reveals complementarity features. 93%
Similar papers in this journal
- 3D modeling of CpG DNA binding with matrix lumican shows leucine-rich repeat motif involvement as in TLR9- CpG DNA interactions 93%
- Binding of different substrate molecules at the docking site and the active site of γ-secretase can trigger toxic events in sporadic and familial Alzheimer's disease 93%
- The molecular mechanism of positive allosteric modulation at the dopamine D1 receptor 92%
Similar papers in this journal
- Design of multi-epitope vaccine candidate against Brucella type IV secretion system (T4SS) 94%
- Framework for analyzing MAE-derived immunopeptidomes from cell lines with shared HLA haplotypes 94%
- Development of an orally-administrable tumor vasculature-targeting therapeutic using annexin A1-binding D-peptides 93%
Similar papers in this journal
- Designing BH3-mimetic Peptide Inhibitors for the Viral Bcl-2 Homologs A179L and BHRF1: Importance of long-range electrostatic interactions 94%
- Exploration of DPP-IV inhibitory peptide design rules assisted by deep learning pipeline that identifies restriction enzyme cutting site 92%
- A self-assembling cross-protective antigen against multiple Gram-positive nosocomial pathogens 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.