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.authorZembe, Lyciasen_ZA
dc.contributor.authorBurgers, Wendy Aen_ZA
dc.contributor.authorJaspan, Heather Ben_ZA
dc.contributor.authorBekker, Linda-Gailen_ZA
dc.contributor.authorBredell, Helbaen_ZA
dc.contributor.authorStevens, Gwynnethen_ZA
dc.contributor.authorGilmour, Jillen_ZA
dc.contributor.authorCox, Josephine Hen_ZA
dc.contributor.authorFast, Patriciaen_ZA
dc.contributor.authorHayes, Peteren_ZA
dc.date.accessioned2015-12-28T06:44:24Z
dc.date.available2015-12-28T06:44:24Z
dc.date.issued2011en_ZA
dc.description.abstractThe 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.identifier.apacitationZembe, 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/11427/16014en_ZA
dc.identifier.chicagocitationZembe, 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/11427/16014en_ZA
dc.identifier.citationZembe, 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.0026096en_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
dc.identifier.urihttp://hdl.handle.net/11427/16014
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0026096
dc.identifier.vancouvercitationZembe 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.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Virologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis 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.holder© 2011 Zembe et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherT cellsen_ZA
dc.subject.otherAntigen presentationen_ZA
dc.subject.otherMajor histocompatibility complexen_ZA
dc.subject.otherHIV-1en_ZA
dc.subject.otherHIVen_ZA
dc.subject.otherEntropyen_ZA
dc.subject.otherImmune responseen_ZA
dc.subject.otherPeptidesen_ZA
dc.titleIntra-and inter-clade cross-reactivity by HIV-1 Gag specific T-cells reveals exclusive and commonly targeted regions: implications for current vaccine trialsen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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