0704-883-0675     |      dataprojectng@gmail.com

COMBINED EXPERIMENTAL AND MODELING STUDIES REVEAL NEW MECHANISMS IN T CELL ANTIGEN RECOGNITION

  • Project Research
  • 1-5 Chapters
  • Abstract : Available
  • Table of Content: Available
  • Reference Style: APA
  • Recommended for : Student Researchers
  • NGN 5000

SUMMARY

T cells of the immune system recognize small antigen peptide fragments loaded onto Major Histocompatibility Complex (MHC) molecules through their T Cell Receptor (TCR). The recognition of antigenic pMHC by the TCR is an extremely sensitive and specific process, discriminating as few as a single antigenic pMHC from the self majority while remaining tolerant to uninfected cells. This unique sensitivity and specificity have been intensely studied, but much is still unknown regarding mechanisms surrounding the antigen recognition process. In the following studies, a Horizontal Atomic Force Microscope (HAFM) was developed to assist in parsing this unique behavior. Utilizing this system, periods of upregulated adhesion, called TCR ligand memory, were investigated between 1E6 TCR and a panel of pMHC of varying potency. The strength of these periods of upregulated adhesion, indicative of an upregulated sensitivity to antigen, inversely correlated with antigen potency. Inhibition of proximal signaling molecule Lck decreased the triggering of these periods, but did not significantly affect their duration. Interestingly, membrane cholesterol oxidation by cholesterol oxidase eliminated TCR ligand memory all together. Treatment with cholesterol sulfate, a naturally occurring analog of cholesterol, depleted TCR ligand memory in a dose-dependent fashion. This behavior was simulated to extract estimates of kinetic parameters and showed that TCRs upregulated their kinetics several magnitudes very quickly upon initial antigen recognition. This mechanism is a way to increase antigenic sensitivity and increase antigen rebinding to further cell activation. xiv Additionally, OT-1 double positive thymocytes were probed by pMHC using a Biomembrane Force Probe (BFP) with different ligands under the presence of CD8, a coreceptor which also binds MHC independently of TCR. Negatively selecting ligands resulted in catch-bonds, and positively selecting ligands resulted in slip bonds. This process relied on the kinase activity of Lck. Simulation-based analysis on these data sets indicated that this mechanism was not the result of passive processes. Force induced formation of long-lived bonds, indicating that mechanical forces are priming formation of a larger complex which enhances lifetime. These bonds dominate the average lifetime and result in catch-bond behavior. Simulations of the BFP assay suggest that mechanotransduction by the TCR resulted in active heterodimerization of CD8 and TCR via interactions between intracellular tails of CD3(TCR) and Lck(CD8). This mechanism results in additional upregulation of binding kinetics for increasing antigen capture and rebinding to promote signaling, thereby also increasing antigen sensitivity and discrimination.




FIND OTHER RELATED TOPICS


Related Project Materials

Development of a Motion Graphics-Based Online Tutorial System for Learning French in Federal University, Dutse, Jigawa State

Background of the Study
Language learning is increasingly leveraging digital technologies to enhance student engagement an...

Read more
An Appraisal of Nurses' Adherence to Patient Confidentiality in Kwara State University Teaching Hospital

Background of the Study

Patient confidentiality is a cornerstone of medical ethics and healthcare pract...

Read more
A review of experiential marketing tactics on consumer engagement at live events: A case study of a music festival in Port Harcourt, Nigeria

Background of the study
Experiential marketing is an innovative approach that engages consumers through immersive, real-lif...

Read more
The impact of government agricultural policies on small-scale cocoa farmers in Ikom Local Government Area, Cross River State.

Background of the study:

Government agricultural policies play a vital role in shaping the fortunes of small-scale cocoa farmers in Ikom....

Read more
An Investigation of the Effectiveness of Psychoeducation in Managing Postpartum Depression: A Case Study of University of Port Harcourt Teaching Hospital, Rivers State

Background of the Study

Postpartum depression (PPD) is a common and serious mental h...

Read more
A critical analysis of programmatic ad buying on consumer engagement: Evidence from a retail brand in Port Harcourt, Nigeria

Background of the study

Programmatic ad buying has transformed the digital advertising landscape by automating the process of purchasing...

Read more
IMPACT OF SOCIAL STUDIES AS CURRICULUM INSTRUMENT IN MINIMIZING VIOLENCE FOR ENHANCING ACADEMIC PERFORMANCE OF JUNIOR SECONDARY SCHOOL STUDENTS IN NIGERIA

ABSTRACT

This research work was conducted with the aim of assessing the impact of Social Studies as curriculum instrument in minimizing v...

Read more
An Exploration of Public Sector Accounting in Revenue Generation for Market Development in Kaduna North LGA, Kaduna State

Background of the Study
Market development is an essential aspect of urban and rural development in Nigeria, with local gov...

Read more
An Evaluation of Semantic Variability in Nigerian Political Communication: A Comparative Study of Debate Transcripts

Background of the Study
Political debates in Nigeria are characterized by a dynamic use of language where semantic variabi...

Read more
The impact of digital transformation on customer service quality in banking: a case study of First Bank of Nigeria

Background of the Study
Digital transformation is fundamentally reshaping customer service paradigms in the banking indust...

Read more
Share this page with your friends




whatsapp