Intra-and inter-clade cross-reactivity by HIV-1 Gag specific T-cells reveals exclusive and commonly targeted regions: implications for current vaccine trials

 

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dc.contributor.author Zembe, Lycias en_ZA
dc.contributor.author Burgers, Wendy A en_ZA
dc.contributor.author Jaspan, Heather B en_ZA
dc.contributor.author Bekker, Linda-Gail en_ZA
dc.contributor.author Bredell, Helba en_ZA
dc.contributor.author Stevens, Gwynneth en_ZA
dc.contributor.author Gilmour, Jill en_ZA
dc.contributor.author Cox, Josephine H en_ZA
dc.contributor.author Fast, Patricia en_ZA
dc.contributor.author Hayes, Peter en_ZA
dc.date.accessioned 2015-12-28T06:44:24Z
dc.date.available 2015-12-28T06:44:24Z
dc.date.issued 2011 en_ZA
dc.identifier.citation Zembe, L., Burgers, W. A., Jaspan, H. B., Bekker, L. G., Bredell, H., Stevens, G., ... & Vardas, E. (2011). Intra-and inter-clade cross-reactivity by HIV-1 Gag specific T-cells reveals exclusive and commonly targeted regions: implications for current vaccine trials. PloS one, 6(10), e26096. doi:10.1371/journal.pone.0026096 en_ZA
dc.identifier.uri http://hdl.handle.net/11427/16014
dc.identifier.uri http://dx.doi.org/10.1371/journal.pone.0026096
dc.description.abstract The genetic diversity of HIV-1 across the globe is a major challenge for developing an HIV vaccine. To facilitate immunogen design, it is important to characterize clusters of commonly targeted T-cell epitopes across different HIV clades. To address this, we examined 39 HIV-1 clade C infected individuals for IFN-γ Gag-specific T-cell responses using five sets of overlapping peptides, two sets matching clade C vaccine candidates derived from strains from South Africa and China, and three peptide sets corresponding to consensus clades A, B, and D sequences. The magnitude and breadth of T-cell responses against the two clade C peptide sets did not differ, however clade C peptides were preferentially recognized compared to the other peptide sets. A total of 84 peptides were recognized, of which 19 were exclusively from clade C, 8 exclusively from clade B, one peptide each from A and D and 17 were commonly recognized by clade A, B, C and D. The entropy of the exclusively recognized peptides was significantly higher than that of commonly recognized peptides (p = 0.0128) and the median peptide processing scores were significantly higher for the peptide variants recognized versus those not recognized (p = 0.0001). Consistent with these results, the predicted Major Histocompatibility Complex Class I IC 50 values were significantly lower for the recognized peptide variants compared to those not recognized in the ELISPOT assay (p<0.0001), suggesting that peptide variation between clades, resulting in lack of cross-clade recognition, has been shaped by host immune selection pressure. Overall, our study shows that clade C infected individuals recognize clade C peptides with greater frequency and higher magnitude than other clades, and that a selection of highly conserved epitope regions within Gag are commonly recognized and give rise to cross-clade reactivities. en_ZA
dc.language.iso eng en_ZA
dc.publisher Public Library of Science en_ZA
dc.rights This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. en_ZA
dc.rights.uri http://creativecommons.org/licenses/by/4.0 en_ZA
dc.source PLoS One en_ZA
dc.source.uri http://journals.plos.org/plosone en_ZA
dc.subject.other T cells en_ZA
dc.subject.other Antigen presentation en_ZA
dc.subject.other Major histocompatibility complex en_ZA
dc.subject.other HIV-1 en_ZA
dc.subject.other HIV en_ZA
dc.subject.other Entropy en_ZA
dc.subject.other Immune response en_ZA
dc.subject.other Peptides en_ZA
dc.title Intra-and inter-clade cross-reactivity by HIV-1 Gag specific T-cells reveals exclusive and commonly targeted regions: implications for current vaccine trials en_ZA
dc.type Journal Article en_ZA
dc.rights.holder © 2011 Zembe et al en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Division of Virology en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation Zembe, L., Burgers, W. A., Jaspan, H. B., Bekker, L., Bredell, H., Stevens, G., ... Hayes, P. (2011). Intra-and inter-clade cross-reactivity by HIV-1 Gag specific T-cells reveals exclusive and commonly targeted regions: implications for current vaccine trials. <i>PLoS One</i>, http://hdl.handle.net/11427/16014 en_ZA
dc.identifier.chicagocitation Zembe, Lycias, Wendy A Burgers, Heather B Jaspan, Linda-Gail Bekker, Helba Bredell, Gwynneth Stevens, Jill Gilmour, Josephine H Cox, Patricia Fast, and Peter Hayes "Intra-and inter-clade cross-reactivity by HIV-1 Gag specific T-cells reveals exclusive and commonly targeted regions: implications for current vaccine trials." <i>PLoS One</i> (2011) http://hdl.handle.net/11427/16014 en_ZA
dc.identifier.vancouvercitation Zembe L, Burgers WA, Jaspan HB, Bekker L, Bredell H, Stevens G, et al. Intra-and inter-clade cross-reactivity by HIV-1 Gag specific T-cells reveals exclusive and commonly targeted regions: implications for current vaccine trials. PLoS One. 2011; http://hdl.handle.net/11427/16014. en_ZA
dc.identifier.ris TY - Journal Article AU - Zembe, Lycias AU - Burgers, Wendy A AU - Jaspan, Heather B AU - Bekker, Linda-Gail AU - Bredell, Helba AU - Stevens, Gwynneth AU - Gilmour, Jill AU - Cox, Josephine H AU - Fast, Patricia AU - Hayes, Peter AB - The genetic diversity of HIV-1 across the globe is a major challenge for developing an HIV vaccine. To facilitate immunogen design, it is important to characterize clusters of commonly targeted T-cell epitopes across different HIV clades. To address this, we examined 39 HIV-1 clade C infected individuals for IFN-γ Gag-specific T-cell responses using five sets of overlapping peptides, two sets matching clade C vaccine candidates derived from strains from South Africa and China, and three peptide sets corresponding to consensus clades A, B, and D sequences. The magnitude and breadth of T-cell responses against the two clade C peptide sets did not differ, however clade C peptides were preferentially recognized compared to the other peptide sets. A total of 84 peptides were recognized, of which 19 were exclusively from clade C, 8 exclusively from clade B, one peptide each from A and D and 17 were commonly recognized by clade A, B, C and D. The entropy of the exclusively recognized peptides was significantly higher than that of commonly recognized peptides (p = 0.0128) and the median peptide processing scores were significantly higher for the peptide variants recognized versus those not recognized (p = 0.0001). Consistent with these results, the predicted Major Histocompatibility Complex Class I IC 50 values were significantly lower for the recognized peptide variants compared to those not recognized in the ELISPOT assay (p<0.0001), suggesting that peptide variation between clades, resulting in lack of cross-clade recognition, has been shaped by host immune selection pressure. Overall, our study shows that clade C infected individuals recognize clade C peptides with greater frequency and higher magnitude than other clades, and that a selection of highly conserved epitope regions within Gag are commonly recognized and give rise to cross-clade reactivities. DA - 2011 DB - OpenUCT DO - 10.1371/journal.pone.0026096 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2011 T1 - Intra-and inter-clade cross-reactivity by HIV-1 Gag specific T-cells reveals exclusive and commonly targeted regions: implications for current vaccine trials TI - Intra-and inter-clade cross-reactivity by HIV-1 Gag specific T-cells reveals exclusive and commonly targeted regions: implications for current vaccine trials UR - http://hdl.handle.net/11427/16014 ER - en_ZA


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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Except where otherwise noted, this item's license is described as This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.