Investigating the molecular mechanisms of chaperones involved in antigen presentation

Devlin, Christine Anne

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

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

Language

eng

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

Handle URL

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

Copyright and License Information

Copyright 2022 Christine Devlin

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