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

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.

journal_name

Eur J Immunol

journal_title

European journal of immunology

authors

Galea I,Stasakova J,Dunscombe MS,Ottensmeier CH,Elliott T,Thirdborough SM

doi

10.1002/eji.201142010

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

256-63

issue

1

eissn

0014-2980

issn

1521-4141

journal_volume

42

pub_type

杂志文章

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