The first step of peptide selection in antigen presentation by MHC class I molecules
Abstract
MHC class I molecules select and present a limited set of peptides from a broad repertoire provided by TAP. How MHC class I makes this selection is unclear. We show that MHC class I H-2Kb molecules initially bind many peptides because of highly flexible binding pockets. Peptide binding is followed by a selection step wherein a large fraction of these peptides is released, leaving the canonical peptides for presentation. The peptide presentation has a remarkable temperature dependency and explains the low-affinity peptides found associated to MHC class I molecules in cells cultured at low temperature. Our data suggest that MHC class I goes through rounds of considering and rejecting peptides until peptides with high affinity are acquired for presentation.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- February 2015
- DOI:
- 10.1073/pnas.1416543112
- Bibcode:
- 2015PNAS..112.1505G