Back to Search
Start Over
Suboptimal stimulation by weak agonist epitope variants does not drive dysfunction of HIV-1-specific cytotoxic T lymphocyte clones
- Source :
- AIDS (London, England). 33(10)
- Publication Year :
- 2019
-
Abstract
- OBJECTIVE: To assess whether weakly recognized epitope variants induce anergy in HIV-1-specific CD8(+) T lymphocyte (CTL) clones as a mechanism of dysfunction. DESIGN: HIV-1-specific CTL clones were exposed to suboptimally recognized epitope variants, and screened for anergy and other T cell dysfunction markers, and subsequent capability to kill target cells bearing index epitope. METHODS: In addition to the optimally recognized index epitope, two suboptimally recognized epitope variants were selected based on titration curves for killing of peptide-labeled target cells by three HIV-1-specific CTL clones targeting the epitopes SLYNTVATL (Gag 77-85, A*02-restricted), RPAEPVPLQL (Rev 66-75, B*07-restricted), and KRWIIMGLNK (Gag 263-272, B*27-restricted). Consequences of suboptimal stimulation were assessed by cytokine secretion, gene expression, and capacity to kill index epitope-labeled target cells upon rechallenge. RESULTS: Suboptimal recognition of epitope variants reduced cytokine production by CTL similarly to reduction in killing of target cells. Gene expression profiles after suboptimal stimulation demonstrated no patterns consistent with T cell dysfunction due to anergy, exhaustion, or apoptosis. Pre-exposure of CTL to epitope variants had no discernable impact on their subsequent capacity to kill index epitope-bearing target cells. CONCLUSIONS: Our data explore the hypothesis that poorly recognized epitope variants not only facilitate HIV-1 evasion of CTL recognition, but also induce CTL dysfunction through suboptimal signaling causing anergy. However, the results do not suggest that suboptimal signaling induces anergy (or exhaustion or apoptosis), indicating that the major role of CTL epitope variation is likely viral escape.
- Subjects :
- 0301 basic medicine
HIV Antigens
medicine.medical_treatment
Immunology
Epitopes, T-Lymphocyte
Stimulation
Biology
Epitope
Article
03 medical and health sciences
0302 clinical medicine
Gene expression
medicine
Immunology and Allergy
Cytotoxic T cell
Humans
030212 general & internal medicine
Cytotoxicity Tests, Immunologic
CTL
030104 developmental biology
Infectious Diseases
Cytokine
Apoptosis
HIV-1
Cytokines
Cytokine secretion
T-Lymphocytes, Cytotoxic
Subjects
Details
- ISSN :
- 14735571
- Volume :
- 33
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- AIDS (London, England)
- Accession number :
- edsair.doi.dedup.....931ebd4e4104a543064f6897376ae6da