T lymphocyte activation is mediated by the interaction of specific TCR with antigenic peptides bound to MHC molecules. Single amino acid substitutions are often capable of changing the effect of a peptide from stimulatory to antagonistic. Using surface plasmon resonance, we have analyzed the interaction between a complex consisting of variants of the MCC peptide bound to a mouse class II MHC (Ek) and a specific TCR. Using both an improved direct binding method as well as a novel inhibition assay, we show that the affinities of three different antagonist peptide-Ek complexes are approximately 10-50 times lower than that of the wildtype MCC-Ek complex for the TCR, largely due to an increased off-rate. These results suggest that the biological effects of peptide antagonists and partial agonists may be largely based on kinetic parameters.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/s1074-7613(00)80309-x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Better Outcomes for Ovarian Cancer Associated With the Detection of Anti-EBV TCR CDR3s: Potential Relevance to Diffuse Large B-Cell Lymphoma.
Am J Reprod Immunol
January 2025
Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.
Objectives: Given the ongoing challenges regarding the specific roles of viral infections in cancer etiology, or as cancer co-morbidities, this study assessed potential associations between anti-viral, T-cell receptor (TCR) complementarity domain region-3 (CDR3s), and clinical outcomes for ovarian cancer.
Methods: TCR CDR3s were isolated from ovarian cancer specimens for a determination of which patients had anti-viral CDR3s and whether those patients had better or worse outcomes.
Results: Analyses revealed that patients with exact matches of anti-Epstein-Barr virus (EBV) CDR3 amino acid sequences exhibited better outcomes for both overall and disease-specific survival.
Identification of novel KRAS neoantigen specific TCRs and a strategy to eliminate off-target recognition.
J Transl Med
January 2025
Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
Background: T cell receptor (TCR)-engineered T cells targeting neoantigens originated from mutations in KRAS gene have demonstrated promising outcomes in clinical trials against solid tumors. However, the challenge lies in developing tumor-specific TCRs that avoid cross-reactivity with self-antigens to minimize the possibility of severe clinical toxicities. Current research efforts have been put towards strategies to eliminate TCR off-target recognition.
View Article and Find Full Text PDFCurrent perspectives and the future of disease-modifying therapies in type 1 diabetes.
World J Diabetes
January 2025
Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Preston PR2 9HT, United Kingdom.
Use of immunomodulating agents to prevent the progression of autoimmune β-cell damage leading to type 1 diabetes mellitus (T1DM) is an interesting area for research. These include non-specific anti-inflammatory agents, immunologic vaccination and anti-inflammatory agents targeting specific immune cells or cytokines. Teplizumab is an anti-CD3-molecule that binds to and leads to the disappearance of the CD3/TCR complex and rendering the T cell anergic to its target antigen.
View Article and Find Full Text PDFRadiomic signatures of brain metastases on MRI: utility in predicting pathological subtypes of lung cancer.
Transl Cancer Res
December 2024
Department of Radiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
Background: The pathological sub-classification of lung cancer is crucial in diagnosis, treatment and prognosis for patients. Quick and timely identification of pathological subtypes from imaging examinations rather than histological tests could help guiding therapeutic strategies. The aim of the study is to construct a non-invasive radiomics-based model for predicting the subtypes of lung cancer on brain metastases (BMs) from multiple magnetic resonance imaging (MRI) sequences.
View Article and Find Full Text PDFA predictive model for advanced esophageal cancer involving the lower third of the esophagus.
Transl Cancer Res
December 2024
College of Life Science, North China University of Science and Technology, Tangshan, China.
Background: Esophageal cancer (EC) is one of the most common malignant tumors worldwide, which has severely threatened human health. This study aims to evaluate the prognostic factors and predictors of survival in patients diagnosed with advanced lower third esophageal carcinoma (aLEC). Based on the Surveillance, Epidemiology, and End Results (SEER) database, we developed a model (nomogram) to provide accurate and individualized survival prediction for the patients who have lost the opportunity to undergo radical surgery.
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!