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Tapasin shapes immunodominance hierarchies according to the kinetic stability of peptide-MHC class I complexes

Record type: Article

Peptide loading of MHC class I molecules involves multiple cofactors including tapasin. We showed previously in vitro that tapasin edits the peptide repertoire by favoring the binding of peptides with slow dissociation rates. Here, using tapasin-deficient mice and a DNA vaccine that primes directly, we confirm that tapasin establishes hierarchical responses in vivo according to peptide-MHC stability. In contrast, this hierarchy is lost when the peptides are cross-presented via an alternative DNA vaccine. By regulating transgene expression, we found that the dominant response modifier was antigen persistence. Our findings reveal strategies for activating T cells against low-affinity peptides, of potential importance for patients with repertoires narrowed by deletional tolerance.

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Citation

Thirdborough, Stephen M., Roddick, Joanne S., Radcliffe, Joanna N., Howarth, Mark, Stevenson, Freda K. and Elliott, Tim (2008) Tapasin shapes immunodominance hierarchies according to the kinetic stability of peptide-MHC class I complexes European Journal of Immunology, 38, (2), pp. 364-369. (doi:10.1002/eji.200737832). (PMID:18196518).

More information

Published date: February 2008
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 368163
URI: http://eprints.soton.ac.uk/id/eprint/368163
ISSN: 0014-2980
PURE UUID: 1acd8a81-ad48-4e5d-ba41-e099e3bf9405
ORCID for Tim Elliott: ORCID iD orcid.org/0000-0003-1097-0222

Catalogue record

Date deposited: 19 Aug 2014 11:03
Last modified: 18 Jul 2017 01:50

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Contributors

Author: Stephen M. Thirdborough
Author: Joanne S. Roddick
Author: Joanna N. Radcliffe
Author: Mark Howarth
Author: Freda K. Stevenson
Author: Tim Elliott ORCID iD

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