Functional avidity-driven activation-induced cell death shapes CTL immunodominance.
J Immunol
; 193(9): 4704-11, 2014 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-25246498
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Ativação Linfocitária
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Linfócitos T Citotóxicos
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Epitopos Imunodominantes
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2014
Tipo de documento:
Article