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

Silvia Dalla Santa, Anna Merlo, Sara Bobisse, Elisa Ronconi, Daniela Boldrin, Gabriella Milan, Vito Barbieri, Oriano Marin, Antonella Facchinetti, Giovanni Biasi, Riccardo Dolcetti, Paola Zanovello, Antonio Rosato

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)4704-4711
Number of pages8
JournalJournal of Immunology
Volume193
Issue number9
DOIs
Publication statusPublished - Nov 1 2014

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Fingerprint Dive into the research topics of 'Functional avidity-driven activation-induced cell death shapes CTL immunodominance'. Together they form a unique fingerprint.

  • Cite this

    Dalla Santa, S., Merlo, A., Bobisse, S., Ronconi, E., Boldrin, D., Milan, G., Barbieri, V., Marin, O., Facchinetti, A., Biasi, G., Dolcetti, R., Zanovello, P., & Rosato, A. (2014). Functional avidity-driven activation-induced cell death shapes CTL immunodominance. Journal of Immunology, 193(9), 4704-4711. https://doi.org/10.4049/jimmunol.1303203