AI Article Synopsis
- HLA-DM is crucial for antigen presentation as it helps remove the CLIP peptide from MHC Class II molecules.
- Competition exists among peptides for binding to MHC Class II, and HLA-DM acts as a "peptide editor" to facilitate peptide swapping.
- Researchers used mutational data and simulations to identify a potential interaction site for HLA-DM and MHC Class II, proposing a dissociation mechanism influenced by an acidic cluster near the peptide's N terminus.
Article Abstract
Human leukocyte antigen (HLA)-DM is a critical participant in antigen presentation that catalyzes the dissociation of the Class II-associated Invariant chain-derived Peptide (CLIP) from the major histocompatibility complex (MHC) Class II molecules. There is competition amongst peptides for access to an MHC Class II groove and it has been hypothesised that DM functions as a 'peptide editor' that catalyzes the replacement of one peptide for another within the groove. It is established that the DM catalyst interacts directly with the MHC Class II but the precise location of the interface is unknown. Here, we combine previously described mutational data with molecular docking and energy minimisation simulations to identify a putative interaction site of >4000A2 which agrees with known point mutational data for both the DR and DM molecule. The docked structure is validated by comparison with experimental data and previously determined properties of protein-protein interfaces. A possible dissociation mechanism is suggested by the presence of an acidic cluster near the N terminus of the bound peptide.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.molimm.2007.07.033 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
One-dimensional nanosonosensitizer boosted multiple branches of immune responses against MHC-deficient immune-evasive urologic tumor.
Sci Adv
January 2025
Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, P. R. China.
Cancer immunotherapies rely on CD8 cytolytic T lymphocytes (CTLs) in recognition and eradication of tumor cells via antigens presented on major histocompatibility complex class I (MHC-I) molecules. However, we observe MHC-I deficiency in human and murine urologic tumors, posing daunting challenges for successful immunotherapy. We herein report an unprecedented nanosonosensitizer of one-dimensional bamboo-like multisegmented manganese dioxide@manganese-bismuth vanadate (BMMBV) to boost multiple branches of immune responses targeting MHC-I-deficient tumors.
View Article and Find Full Text PDFAntigen processing and presentation via major histocompatibility complex (MHC) molecules are central to immune surveillance. Yet, quantifying the dynamic activity of MHC class I and II antigen presentation remains a critical challenge, particularly in diseases like cancer, infection and autoimmunity where these pathways are often disrupted. Current methods fall short in providing precise, sample-specific insights into antigen presentation, limiting our understanding of immune evasion and therapeutic responses.
View Article and Find Full Text PDFMAIT Cell-Mediated Immune Mechanisms of Dialysis-Induced Peritoneal Fibrosis and Therapeutic Targeting.
J Am Soc Nephrol
January 2025
Nephrology Division, Department of Medicine, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
Background: Peritoneal fibrosis is a serious complication of long-term peritoneal dialysis (PD) and abdominal surgeries, yet effective treatments remain elusive. Given the known roles of mucosal-associated invariant T (MAIT) cells in immune responses and fibrotic diseases, we investigated their involvement in PD-induced peritoneal fibrosis to identify potential therapeutic targets.
Methods: We employed single-cell RNA sequencing (scRNA-seq) and flow cytometry to characterize the activation and function of peritoneal MAIT cells in patients undergoing long-term PD.
Glia Modulates Immune Responses in the Retina Through Distinct MHC Pathways.
Glia
January 2025
Department of Ophthalmology, Bern University Hospital and Department of BioMedical Research, University of Bern, Bern, Switzerland.
Glia antigen-presenting cells (APCs) are pivotal regulators of immune surveillance within the retina, maintaining tissue homeostasis and promptly responding to insults. However, the intricate mechanisms underlying their local coordination and activation remain unclear. Our study integrates an animal model of retinal injury, retrospective analysis of human retinas, and in vitro experiments to gain insights into the crucial role of antigen presentation in neuroimmunology during retinal degeneration (RD), uncovering the involvement of various glial cells, notably Müller glia and microglia.
View Article and Find Full Text PDFSingle-cell RNA-seq reveals immune cell heterogeneity and increased Th17 cells in human fibrotic skin diseases.
Front Immunol
January 2025
Dermatology Hospital, Southern Medical University, Guangzhou, China.
Background: Fibrotic skin disease represents a major global healthcare burden, characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix components. The immune cells are postulated to exert a pivotal role in the development of fibrotic skin disease. Single-cell RNA sequencing has been used to explore the composition and functionality of immune cells present in fibrotic skin diseases.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!