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Proc Natl Acad Sci U S A. 2015 Jan 6;112(1):202-7. doi: 10.1073/pnas.1418690112. Epub 2014 Dec 22.

Dipeptides catalyze rapid peptide exchange on MHC class I molecules.

Author information

1
Molecular Life Science, Jacobs University Bremen, 28759 Bremen, Germany; and.
2
Department of Immunology, Eberhard Karls University Tübingen, 72076 Tübingen, Germany.
3
Molecular Life Science, Jacobs University Bremen, 28759 Bremen, Germany; and sebastian.springer@queens.oxon.org.

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.

KEYWORDS:

MHC tetramers; dipeptides; immunotherapy; peptide exchange; tapasin

PMID:
25535340
PMCID:
PMC4291614
DOI:
10.1073/pnas.1418690112
[Indexed for MEDLINE]
Free PMC Article

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