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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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.
|Digital Object Identifier (DOI):||doi:10.1002/eji.200737832|
|Subjects:||R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)|
|Date Deposited:||19 Aug 2014 11:03|
|Last Modified:||19 Feb 2017 22:08|
Funded by: CRUK (UNSPECIFIED)
UNSPECIFIED to UNSPECIFIED
|Further Information:||Google Scholar|
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