Article: article from journal or magazin.
Functional avidity-driven activation-induced cell death shapes CTL immunodominance.
Journal of Immunology (baltimore, Md. : 1950)
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
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.
Animals, Antigens, Viral/immunology, Apoptosis/immunology, Cell Line, Cytotoxicity, Immunologic, Female, Gene Products, env/immunology, Gene Products, gag/immunology, Humans, Immunodominant Epitopes/immunology, Lymphocyte Activation/immunology, Mice, Retroviridae/immunology, T-Lymphocyte Subsets/immunology, T-Lymphocyte Subsets/metabolism, T-Lymphocytes, Cytotoxic/immunology, T-Lymphocytes, Cytotoxic/metabolism
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