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Dipeptides catalyze rapid peptide exchange on MHC class I molecules

Author:
Saini, Sunil Kumar, Schuster, Heiko, Ramnarayan, Venkat Raman, Rammensee, Hans-Georg, Stevanović, Stefan, Springer, Sebastian
Source:
Proceedings of the National Academy of Sciences of the United States of America 2015 v.112 no.1 pp. 202-207
ISSN:
0027-8424
Subject:
dipeptides, dissociation, epitopes, immunotherapy, neoplasm cells, neoplasms
Abstract:
Peptide ligand selection by MHC class I molecules, which occurs by iterative optimization, is the centerpiece of immunodominance in antiviral and antitumor immune responses. For its understanding, the molecular mechanisms of peptide binding and dissociation by class I molecules must be elucidated. To this end, we have investigated dipeptides that bind to the F pocket of class I molecules. We find that they accelerate the dissociation of prebound peptides of both low and high affinity, suggesting a mechanism of action for the peptide-exchange chaperone tapasin. Peptide exchange on class I molecules also has practical uses in epitope discovery and T-cell monitoring.
Agid:
2304388