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


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).

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Description/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.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1002/eji.200737832
ISSNs: 0014-2980 (print)
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Organisations: Cancer Sciences
ePrint ID: 368163
Date :
Date Event
February 2008Published
Date Deposited: 19 Aug 2014 11:03
Last Modified: 19 Feb 2017 22:08
Projects:
UNSPECIFIED
Funded by: CRUK (UNSPECIFIED)
UNSPECIFIED to UNSPECIFIED
Further Information:Google Scholar
URI: http://eprints.soton.ac.uk/id/eprint/368163

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