Title page for ETD etd-06062011-125030


Document Type Master's Dissertation
Author Smidt, Werner
Email werner.smidt@gmail.com
URN etd-06062011-125030
Document Title In silico inference of immunological relationship between protein antigens based on their cytotoxic T-lymphocyte epitope repertoires
Degree MSc
Department Bioinformatics
Supervisor
Advisor Name Title
Mr F Joubert Supervisor
Keywords
  • infections
  • CTL
  • Cytotoxic T-Cell
  • molecules
Date 2011-04-07
Availability unrestricted
Abstract
The importance of Cytotoxic T-Cell (CTL) reponses during the course of intracellular infections has received a lot of attention during the past few decades. CTLs respond to epitopes presented by the Major Histocompatibility Complex (MHC) originating from intracellular proteins for which they have an appropriate T-Cell Receptor (TCR) for. This response is crucial for the control of pathogens such as Influenza, Hepatitis, HIV and others by destroying the cell in which the pathogen replicates. Due to the extreme polymorphism of MHC molecules, Computational Immunology techniques have been developed to detect potential MHC ligands and as a consequence, potential CTL epitopes. The polymorphism factor needs to be taken into account especially when concerning the design of vaccines with a CTL response component to maximize population coverage. Tools have been constructed that combine the predictions tools concerning major steps in this pathway, that is, proteasomal cleavage, Transporter associated with Antigen Presentation (TAP) affinity, Major Histocompatibility Complex (MHC) affinity and Immunogenicity. In this study, a novel method is developed to combine the different steps in the pathway, which includes the development of a novel TAP predictor. Furthermore, by using a BLOSUM-based score in conjunction with the epitope prediction results, a novel CTL epitopebased clustering method was developed. Two pathogens with major CTL epitope components, but vastly different mutation rates were chosen to infer whether the aforementioned methods can be used to detect potential CTL epitopes and group sequences together based on shared immunogenicity.

2010, University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria.

Please cite as follows:

Smidt, W 2010, In silico inference of immunological relationship between protein antigens based on their cytotoxic T-lymphocyte epitope repertoires, MSc dissertation, University of Pretoria, Pretoria, viewed yymmdd < http://upetd.up.ac.za/thesis/available/etd-06062011-125030 / >

E11/383/gm

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