Clonotypic architecture of a Gag-specific CD8+ T-cell response in chronic human HIV-2 infection.
Eirini MoysiSamuel DarkoEster Gea-MallorquíConstantinos PetrovasJorge R AlmeidaDavid WolinskyYanchun PengAssan JayeGuillaume Stewart-JonesDaniel C DouekRichard A KoupTao DongSarah L Rowland-JonesPublished in: European journal of immunology (2021)
The dynamics of T-cell receptor (TCR)selection in chronic HIV-1 infection, and its association with clinical outcome, is well documented for an array of MHC-peptide complexes and disease stages. However, the factors that may contribute to the selection and expansion of CD8+ T-cells in chronic HIV-2 infection, especially at the clonal level remain unclear. To address this question, we undertook a detailed molecular characterization of the clonotypic architecture of an HLA-B*3501 restricted Gag-specific CD8+ T-cell response in donors chronically infected with HIV-2 using a combination of flow cytometry, tetramer-specific CD8+ TCR clonotyping, and in vitro assays. We show that the response to the NY9 epitope is hierarchical and narrow in terms of T-cell receptor-alpha (TCRA) and -beta (TCRB) gene usage yet clonotypically diverse. Furthermore, clonotypic dominance in shared origin CTL clones was associated with a greater magnitude of cytokine production and antigen sensitivity at limiting antigen dilution as well as enhanced cross-reactivity for known HIV-2 variants. Hence, our data suggest that effector mobilization and expansion in human chronic HIV-2 infection may be linked to the qualitative features of specific CD8+ T-cell clonotypes, which could have implications for viral control and disease outcome.
Keyphrases
- antiretroviral therapy
- hiv infected
- hiv positive
- human immunodeficiency virus
- flow cytometry
- endothelial cells
- regulatory t cells
- hiv aids
- hiv testing
- hepatitis c virus
- systematic review
- copy number
- men who have sex with men
- induced pluripotent stem cells
- pluripotent stem cells
- machine learning
- high throughput
- drug induced
- electronic health record
- liquid chromatography tandem mass spectrometry
- artificial intelligence