Investigating the molecular mechanisms of chaperones involved in antigen presentation

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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biochemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2022

Author dc:creator

• Devlin, Christine Anne

Contributors dc:contributor

• Procko, Erik
• Kranz, David
• Stadtmueller, Beth
• Nair, Satish

• immunology
• protein

Statement dc:rights

• Copyright 2022 Christine Devlin

Language dc:language

en, eng

Handle dc:identifier

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

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F117887