Menu
Close

Special Seminar: Dr. Andrew McShan

Room: 
https://bluejeans.com/764447847
Date: 
Tuesday, January 25, 2022 - 4:00pm to 5:00pm
"Finding Cinderella’s Slipper:​ How Immunological Chaperones Charm Antigens onto the MHC-I to Fight Disease"

Immune chaperones tapasin and TAPBPR associate with class I major histocompatibility complex (MHC-I) molecules to
promote loading, exchange, and editing of peptide antigen cargo. The resulting peptide/MHC-I complexes display antigens to
cytotoxic T cells on the cell surface for immune surveillance. Insights into peptide/MHC-I antigen presentation are important given
that it is the most critical pathway used by the immune system to sense and respond to cancer, pathogen infection, and
autoimmune disease. While several recently solved peptide-deficient MHC-I/chaperone structures provide important insights
through static snapshots, a complete understanding of how immune chaperones contribute to antigen selection and presentation
remains elusive. Here, using solution NMR and complementary biophysical assays, we investigate the molecular mechanism of
peptide loading, selection, and exchange on the 90 kDa MHC-I/TAPBPR complex. We further explore the role of protein dynamics
in shaping chaperone specificity towards different human MHC allotypes, which vary from person to person in the population and
determine disease susceptibility. In addition, we uncover a functional role for a TAPBPR loop that directly senses and traps
peptides antigen on the MHC-I groove. Finally, we examine whether TAPBPR contributes to metabolite antigen presentation by the
non-classical MHC-I related molecule MR1 and compare our results to the classical peptide/MHC-I system. Together, our findings
enable us to define similarities and differences utilized by immune chaperones to dictate peptide and metabolite antigen
presentation by the MHC-I versus MR1. 

Contact Information: 
Host:  Amit Reddi
Map of Georgia Tech

School of Chemistry & Biochemistry

901 Atlantic Drive Atlanta, GA 30332-0400

(404) 894-4002 (phone) | (404) 894-7452 (fax)