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@article{Hayes:2021:10.1371/journal.pone.0260118,
author = {Hayes, P and Fernandez, N and Ochsenbauer, C and Dalel, J and Hare, J and King, D and Black, L and Streatfield, C and Kakarla, V and Macharia, G and Makinde, J and Price, M and Hunter, E and IAVI, protocol C investigators and Gilmour, J},
doi = {10.1371/journal.pone.0260118},
journal = {PLoS One},
pages = {1--24},
title = {Breadth of CD8 T-cell mediated inhibition of replication of diverse HIV-1 transmitted-founder isolates correlates with the breadth of recognition within a comprehensive HIV-1 Gag, Nef, Env and Pol potential T-cell epitope (PTE) peptide set.},
url = {http://dx.doi.org/10.1371/journal.pone.0260118},
volume = {16},
year = {2021}
}

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TY  - JOUR
AB  - Full characterisation of functional HIV-1-specific T-cell responses, including identification of recognised epitopes linked with functional antiviral responses, would aid development of effective vaccines but is hampered by HIV-1 sequence diversity. Typical approaches to identify T-cell epitopes utilising extensive peptide sets require subjects' cell numbers that exceed feasible sample volumes. To address this, CD8 T-cells were polyclonally expanded from PBMC from 13 anti-retroviral naïve subjects living with HIV using CD3/CD4 bi-specific antibody. Assessment of recognition of individual peptides within a set of 1408 HIV-1 Gag, Nef, Pol and Env potential T-cell epitope peptides was achieved by sequential IFNγ ELISpot assays using peptides pooled in 3-D matrices followed by confirmation with single peptides. A Renilla reniformis luciferase viral inhibition assay assessed CD8 T-cell-mediated inhibition of replication of a cross-clade panel of 10 HIV-1 isolates, including 9 transmitted-founder isolates. Polyclonal expansion from one frozen PBMC vial provided sufficient CD8 T-cells for both ELISpot steps in 12 of 13 subjects. A median of 33 peptides in 16 epitope regions were recognised including peptides located in previously characterised HIV-1 epitope-rich regions. There was no significant difference between ELISpot magnitudes for in vitro expanded CD8 T-cells and CD8 T-cells directly isolated from PBMCs. CD8 T-cells from all subjects inhibited a median of 7 HIV-1 isolates (range 4 to 10). The breadth of CD8 T-cell mediated HIV-1 inhibition was significantly positively correlated with CD8 T-cell breadth of peptide recognition. Polyclonal CD8 T-cell expansion allowed identification of HIV-1 isolates inhibited and peptides recognised within a large peptide set spanning the major HIV-1 proteins. This approach overcomes limitations associated with obtaining sufficient cell numbers to fully characterise HIV-1-specific CD8 T-cell responses by different functiona
AU  - Hayes,P
AU  - Fernandez,N
AU  - Ochsenbauer,C
AU  - Dalel,J
AU  - Hare,J
AU  - King,D
AU  - Black,L
AU  - Streatfield,C
AU  - Kakarla,V
AU  - Macharia,G
AU  - Makinde,J
AU  - Price,M
AU  - Hunter,E
AU  - IAVI,protocol C investigators
AU  - Gilmour,J
DO  - 10.1371/journal.pone.0260118
EP  - 24
PY  - 2021///
SN  - 1932-6203
SP  - 1
TI  - Breadth of CD8 T-cell mediated inhibition of replication of diverse HIV-1 transmitted-founder isolates correlates with the breadth of recognition within a comprehensive HIV-1 Gag, Nef, Env and Pol potential T-cell epitope (PTE) peptide set.
T2  - PLoS One
UR  - http://dx.doi.org/10.1371/journal.pone.0260118
UR  - https://www.ncbi.nlm.nih.gov/pubmed/34788349
UR  - https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0260118
UR  - http://hdl.handle.net/10044/1/93019
VL  - 16
ER  -

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