| First Author | Galea I | Year | 2012 |
| Journal | Eur J Immunol | Volume | 42 |
| Issue | 1 | Pages | 256-63 |
| PubMed ID | 22002320 | Mgi Jnum | J:179828 |
| Mgi Id | MGI:5304224 | Doi | 10.1002/eji.201142010 |
| Citation | Galea I, et al. (2012) CD8(+) T-cell cross-competition is governed by peptide-MHC class I stability. Eur J Immunol 42(1):256-63 |
| abstractText | 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. |
