Tapasin shapes immunodominance hierarchies according to the kinetic stability of peptide-MHC class I complexes
Tapasin shapes immunodominance hierarchies according to the kinetic stability of peptide-MHC class I complexes
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.
364-369
Thirdborough, Stephen M.
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Roddick, Joanne S.
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Radcliffe, Joanna N.
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Howarth, Mark
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Stevenson, Freda K.
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Elliott, Tim
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February 2008
Thirdborough, Stephen M.
db1c7877-e63c-42e0-ba07-72fbf27a32f2
Roddick, Joanne S.
dddd0a9c-ef7a-4cb4-810d-8927ff1ce76f
Radcliffe, Joanna N.
95bba459-28f5-46d5-b1f1-8e077f115e52
Howarth, Mark
9b79b039-8294-4326-be62-4a72b7c60f8e
Stevenson, Freda K.
0e44106e-1438-44e0-8d3f-bde83a16318f
Elliott, Tim
16670fa8-c2f9-477a-91df-7c9e5b453e0e
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), .
(doi:10.1002/eji.200737832).
(PMID:18196518)
Abstract
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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Published date: February 2008
Organisations:
Cancer Sciences
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Local EPrints ID: 368163
URI: http://eprints.soton.ac.uk/id/eprint/368163
ISSN: 0014-2980
PURE UUID: 1acd8a81-ad48-4e5d-ba41-e099e3bf9405
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Date deposited: 19 Aug 2014 11:03
Last modified: 15 Mar 2024 03:08
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Author:
Stephen M. Thirdborough
Author:
Joanne S. Roddick
Author:
Joanna N. Radcliffe
Author:
Mark Howarth
Author:
Freda K. Stevenson
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