CD8(+) T-cell cross-competition is governed by peptide-MHC class I stability


Galea, Ian, Stasakova, Jana, Dunscombe, Melanie S., Ottensmeier, Christian H., Elliott, Tim and Thirdborough, Stephen M. (2011) CD8(+) T-cell cross-competition is governed by peptide-MHC class I stability European Journal of Immunology, 42, (1), pp. 256-263. (doi:10.1002/eji.201142010). (PMID:22002320).

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Description/Abstract

A major contributing factor to the final magnitude and breadth of CD8+ T-cell responses to complex antigens is immunodomination, where CD8+ T cells recognizing their cognate ligand inhibit the proliferation of other CD8+ T cells engaged with the same APC. In this study, we examined how the half-life of cell surface peptide–MHC class I complexes influences this phenomenon. We found that primary CD8+ T-cell responses to DNA vaccines in mice are shaped by competition among responding CD8+ T cells for nonspecific stimuli early after activation and prior to cell division. The susceptibility of CD8+ T cells to ‘domination’ was a direct correlate of higher kinetic stability of the competing CD8+ T-cell cognate ligand. When high affinity competitive CD8+ T cells were deleted by self-antigen expression, competition was abrogated. These findings show, for the first time to our knowledge, the existence of regulatory mechanisms that direct the responding CD8+ T-cell repertoire toward epitopes with high-stability interactions with MHC class I molecules. They also provide an insight into factors that facilitate CD8+ T-cell coexistence, with important implications for vaccine design and delivery.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1002/eji.201142010
ISSNs: 0014-2980 (print)
Keywords: cd8+ t cells, competition, immunodominance, mhc, peptide
Subjects: Q Science > QR Microbiology > QR180 Immunology
Organisations: Clinical & Experimental Sciences
ePrint ID: 204417
Date :
Date Event
28 November 2011e-pub ahead of print
January 2012Published
Date Deposited: 28 Nov 2011 14:43
Last Modified: 23 Feb 2017 17:01
Projects:
UNSPECIFIED
Funded by: Wellcome Trust CRUK (UNSPECIFIED)
UNSPECIFIED to UNSPECIFIED
Further Information:Google Scholar
URI: http://eprints.soton.ac.uk/id/eprint/204417

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