Functional avidity-driven activation-induced cell death shapes CTL immunodominance

Dalla Santa, Silvia, Merlo, Anna, Bobisse, Sara, Ronconi, Elisa, Boldrin, Daniela, Milan, Gabriella, Barbieri, Vito, Marin, Oriano, Facchinetti, Antonella, Biasi, Giovanni, Dolcetti, Riccardo, Zanovello, Paola and Rosato, Antonio (2014) Functional avidity-driven activation-induced cell death shapes CTL immunodominance. Journal of Immunology, 193 9: 4704-4711. doi:10.4049/jimmunol.1303203


Author Dalla Santa, Silvia
Merlo, Anna
Bobisse, Sara
Ronconi, Elisa
Boldrin, Daniela
Milan, Gabriella
Barbieri, Vito
Marin, Oriano
Facchinetti, Antonella
Biasi, Giovanni
Dolcetti, Riccardo
Zanovello, Paola
Rosato, Antonio
Title Functional avidity-driven activation-induced cell death shapes CTL immunodominance
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 1550-6606
0022-1767
Publication date 2014-11-01
Year available 2014
Sub-type Article (original research)
DOI 10.4049/jimmunol.1303203
Open Access Status Not yet assessed
Volume 193
Issue 9
Start page 4704
End page 4711
Total pages 8
Place of publication Bethesda, United States
Publisher American Association of Immunologists
Language eng
Formatted abstract
Immunodominance is a complex phenomenon that relies on a mere numerical concept, while being potentially influenced at every step of the immune response. We investigated the mechanisms leading to the establishment of CTL immunodominance in a retroviral model and found that the previously defined subdominant Env-specific CD8+ T cells are endowed with an unexpectedly higher functional avidity than is the immunodominant Gag-recognizing counterpart. This high avidity, along with the Env Ag overload, results in a supraoptimal TCR engagement. The overstimulation makes Env-specific T lymphocytes more susceptible to apoptosis, thus hampering their expansion and leading to an unintentional “immune kamikazing.” Therefore, Ag-dependent, hyperactivation-induced cell death can be regarded as a novel mechanism in the establishment of the immunodominance that restrains and opposes the expansion of high-avidity T cells in favor of lower-affinity populations.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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