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Published on: May 6, 2019
[Immunodominance in CD8+ T cell responses to HIV-1 synthesized epitopes]
Yang-Bo Tang1, Xiao-Ping Tang, Xia Jin
1Institute of infectious diseases, Guangzhou Eighth People's Hospital, Guangzhou, China. yangbotang@tom.com
Insights
Human immunodeficiency virus type 1 (HIV-1) Gag peptides elicit dominant CD8+ T cell responses. CFSE labeling and flow cytometry offer a complementary method to ELISPOT for assessing HIV-1 T cell immunodominance.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Understanding CD8+ T cell responses to human immunodeficiency virus type 1 (HIV-1) is crucial for vaccine development.
- Immunodominance, the preferential response to certain epitopes, shapes the overall immune landscape.
- Long-term nonprogressors (LTNPs) provide valuable insights into effective HIV-1 immune control.
Observation:
- HIV-1 Gag peptides induced the strongest Interferon-gamma (IFN-gamma) secreting CD8+ T cell responses in LTNP PBMCs.
- Nef, Tat, and Vif peptides showed moderate responses, while Env and Pol peptides elicited minimal responses.
- Both ELISPOT and CFSE labeling assays demonstrated a proportional relationship between IFN-gamma secretion and CD8+ T cell proliferation.
Findings:
- HIV-1 Gag epitopes are immunodominant targets for CD8+ T cell responses in LTNPs.
- The frequency of IFN-gamma secreting cells correlated with CD8+ T cell proliferation.
- CFSE labeling and flow cytometry serve as a viable alternative to ELISPOT for evaluating HIV-1 specific T cell proliferation.
Implications:
- Identifying immunodominant HIV-1 epitopes can guide the design of more effective T cell-based vaccines.
- CFSE labeling offers a novel, complementary approach for studying HIV-1 specific CD8+ T cell immunodominance.
- Further research into the mechanisms of Gag-specific T cell responses may reveal strategies for controlling HIV-1 infection.
Objective:
To investigate immunodominance in CD8+ T cell responses to human immunodeficiency virus type 1 (HIV-1) epitopes.
Methods:
Frequency of Interferon-gamma (IFN-gamma) secreting cells and the proliferation percentage of CD8+ T cells in PBMC from an HIV-1-infected long term nonprogressor (LTNP) were assessed after stimulation with either the 34 pools of 701 overlapping peptides covering the regions of HIV-1 Env, Pol, Gag, Vif, Nef, Tat or some single peptides, by using various assays including enzyme-linked immunospot (ELISPOT) and CFSE Carboxy-fluorescein diacetate, succinimidyl ester (CFSE) labeling and flow cytometry.
Results:
HIV-1 Gag peptides induced the highest frequency of IFN-gamma secreting cells, followed by Nef, Tat, and Vif. Meanwhile, Env and Pol failed to induce significant responses. In the IFN-gamma ELISPOT assay, stimulation with single peptide and the corresponsive peptide pool generated analogous results. In addition, the frequencies of IFN-gamma secreting cells and the proliferation percentage of CD8+ T cells detected-ELISPOT and CFSE labeling and flow cytometry were proportional, when single peptides were used for stimulation.
Conclusion:
CD8+ T cells can respond to some specific HIV-1 epitopes and induce immunodominant responses. As a complimentary approach to the standard of ELISPOT assay, We recommend a novel CFSE labeling and flow cytometry assay for the examination of immunodominance in studies of HIV-1 specific proliferation percentage of CD8+ T cell responses.
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