Developing a System to Determine Proper Peptide Binding in Class II Major Histocompatability Complex Molecules

Persistent Link:
http://hdl.handle.net/10150/245083
Title:
Developing a System to Determine Proper Peptide Binding in Class II Major Histocompatability Complex Molecules
Author:
Vasic, Jelena
Issue Date:
Aug-2012
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Embargo:
Item Not Available
Abstract:
The T-cell compartment of the adaptive immune system executes a critical role in human health by taking advantage of combinatorial diversity to recognize virtually any antigen. Upon infection, dendritic cells (DCs) use major histocompatibility complex (MHC) molecules to present antigenic peptides to T-cell receptors (TCR) on T-cells. TCR are then able to recognize the composite surface of peptide- MHC (pMHC) complexes and pass this information into the T-cell, thus linking the innate and adaptive immune systems. CD4⁺ T-cells then play a fundamental role in directing and regulating the immune response to a pathogen. A significant decline in immune system function and an increased susceptibility to infections from pathogens such as West Nile Virus (WNV) is seen upon aging. We hypothesized that this may be due to a reduced frequency of CD4⁺ T-cells that are specific for, and capable of responding to, WNV. To quantify these frequencies we have developed pMHC II tetramers, a powerful tool for characterizing the T-cell repertoire and one that has been a challenge to produce. The development of these tetramers hinges on the ability of the peptide fragment to bind properly to the MHC molecule. It is therefore beneficial to have a system for optimizing peptide selection prior to beginning the elaborate tetramer building process. We have engineered retroviral constructs encoding IAᵇ α and β chains, and we plan on using these constructs to stably transduce M12 cells. We will use cell surface expression of IAᵇ molecules as readout for proper pMHC II complex folding. The goal of the project is to develop a cost-effective system to optimize binding of a variety of peptides to MHC II molecule to aid the development of pMHC II tetramers.
Type:
text; Electronic Thesis
Degree Name:
B.S.
Degree Level:
bachelors
Degree Program:
Honors College; Molecular and Cellular Biology
Degree Grantor:
University of Arizona

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleDeveloping a System to Determine Proper Peptide Binding in Class II Major Histocompatability Complex Moleculesen_US
dc.creatorVasic, Jelenaen_US
dc.contributor.authorVasic, Jelenaen_US
dc.date.issued2012-08-
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.releaseItem Not Available-
dc.description.abstractThe T-cell compartment of the adaptive immune system executes a critical role in human health by taking advantage of combinatorial diversity to recognize virtually any antigen. Upon infection, dendritic cells (DCs) use major histocompatibility complex (MHC) molecules to present antigenic peptides to T-cell receptors (TCR) on T-cells. TCR are then able to recognize the composite surface of peptide- MHC (pMHC) complexes and pass this information into the T-cell, thus linking the innate and adaptive immune systems. CD4⁺ T-cells then play a fundamental role in directing and regulating the immune response to a pathogen. A significant decline in immune system function and an increased susceptibility to infections from pathogens such as West Nile Virus (WNV) is seen upon aging. We hypothesized that this may be due to a reduced frequency of CD4⁺ T-cells that are specific for, and capable of responding to, WNV. To quantify these frequencies we have developed pMHC II tetramers, a powerful tool for characterizing the T-cell repertoire and one that has been a challenge to produce. The development of these tetramers hinges on the ability of the peptide fragment to bind properly to the MHC molecule. It is therefore beneficial to have a system for optimizing peptide selection prior to beginning the elaborate tetramer building process. We have engineered retroviral constructs encoding IAᵇ α and β chains, and we plan on using these constructs to stably transduce M12 cells. We will use cell surface expression of IAᵇ molecules as readout for proper pMHC II complex folding. The goal of the project is to develop a cost-effective system to optimize binding of a variety of peptides to MHC II molecule to aid the development of pMHC II tetramers.en_US
dc.typetexten_US
dc.typeElectronic Thesisen_US
thesis.degree.nameB.S.en_US
thesis.degree.levelbachelorsen_US
thesis.degree.disciplineHonors Collegeen_US
thesis.degree.disciplineMolecular and Cellular Biologyen_US
thesis.degree.grantorUniversity of Arizonaen_US
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