University of Illinois Urbana-Champaign

Investigating the molecular mechanisms of chaperones involved in antigen presentation

Devlin, Christine Anne

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https://hdl.handle.net/2142/117887

Description

Title
Investigating the molecular mechanisms of chaperones involved in antigen presentation
Author(s)
Devlin, Christine Anne
Issue Date
2022-06-14
Director of Research (if dissertation) or Advisor (if thesis)
Procko, Erik
Doctoral Committee Chair(s)
Procko, Erik
Committee Member(s)
  • Kranz, David
  • Stadtmueller, Beth
  • Nair, Satish
Department of Study
Biochemistry
Discipline
Biochemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
immunology, protein
Abstract
Class I major histocompatibility complexes (MHC-I) play an important role in the adaptive immune system as they present peptides on the cell surface. Peptides from non-self proteins can be recognized by surveilling T cells leading to cell lysis. The mechanism of peptide loading, termed antigen presentation, by chaperones, tapasin and TAPBPR, is unclear. Here, using biochemical and biophysical assays, I characterize the mechanism of TAPBPR, a chaperone and peptide editor that is independent of the peptide loading complex. First, I show that TAPBPR can bind as a chaperone with broad MHC-I allelic recognition but has narrow MHC-I specificity in regard to peptide editing. Additionally, there is a folded protein motif within the α2 helix of the MHC-I that TAPBPR is recognizing to bind as a chaperone. Second, I show that the proposed “scoop loop” of TAPBPR is unimportant for chaperoning ability and show that the important regions of TAPBPR for this activity are located where the protein interacts with the base of the MHC-I α2 helix as Ill as beta-2-microglobulin. Third, I engineered a version of TAPBPR with dual functions of chaperone and peptide editor of multiple HLA-A alleles. Overall, this work provides further insight into the mechanisms involved in antigen presentation.
Graduation Semester
2022-08
Type of Resource
Thesis
Copyright and License Information
Copyright 2022 Christine Devlin

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