Novel and promiscuous CTL epitopes in conserved regions of Gag targeted by individuals with early subtype C HIV type 1 infection from Southern Africa

Agatha M. Masemola, Tumelo N. Mashishi, Greg Khoury, Helba Bredell, Maria Paximadis, Tiyani Mathebula, Debra Barkhan, Adrian Puren, Efthyia Vardas, Mark Colvin, Lynn Zijenah, David Katzenstein, Rosemary Musonda, Susan Allen, Newton Kumwenda, Taha E Taha, Glenda Gray, James McIntyre, Salim Abdool Karim, Haynes W. Sheppard & 20 others Clive M. Gray, Michelle Klautzman, Newton Kumwenda, Victoria Aquino, Michael Chirenje, Mike Mbizo, Ocean Tobaiwa, Armstrong Mafhandu, Dudu Msweli, Wendy Dlamini, Gita Ramjee, Quarraisha Abdool Karim, Lynn Morris, Natasha Taylor, Carolyn Williamson, Celia Rademayer, Jorge Flores, Ward Cates, Linda McNeil, Missie Allen

Research output: Contribution to journalArticle

Abstract

Characterization of optimal CTL epitopes in Gag can provide crucial information for evaluation of candidate vaccines in populations at the epicenter of the HIV-1 epidemic. We screened 38 individuals with recent subtype C HIV-1 infection using overlapping consensus C Gag peptides and hypothesized that unique HLA-restricting alleles in the southern African population would determine novel epitope identity. Seventy-four percent of individuals recognized at least one Gag peptide pool. Ten epitopic regions were identified across p17, p24, and p2p7p1p6, and greater than two-thirds of targeted regions were directed at: TGTEELRSLYN TVATLY (p17, 35%); GPKEPFRDYVDRFFKTLRAEQATQDV (p24, 19%); and RGGKLDKWEKIRLRPGGKKHYMLKHL (p17, 15%). After alignment of these epitopic regions with consensus M and a consensus subtype C sequence from the cohort, it was evident that the regions targeted were highly conserved. Fine epitope mapping revealed that five of nine identified optimal Gag epitopes were novel: HLVWASREL, LVWASRELERF, LYNTVATLY, PFRDYVDRFF, and TLRAEQATQD, and were restricted by unique HLA-Cw*08, HLA-A*30/B*57, HLA-A*29/B*44, and HLA-Cw*03 alleles, respectively. Notably, three of the mapped epitopes were restricted by more than one HLA allele. Although these epitopes were novel and restricted by unique HLA, they overlapped or were embedded within previously described CTL epitopes from subtype B HIV-1 infection. These data, emphasize the promiscuous nature of epitope binding and support our hypothesis that HLA diversity between populations can shape line epitope identity, but may not represent a constraint for universal recognition of Gag in highly conserved domains.

Original languageEnglish (US)
Pages (from-to)4607-4617
Number of pages11
JournalJournal of Immunology
Volume173
Issue number7
StatePublished - Oct 1 2004

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Southern Africa
HIV Infections
HIV-1
Epitopes
Alleles
Population
Epitope Mapping
Peptides
HLA-A Antigens
Vaccines

ASJC Scopus subject areas

  • Immunology

Cite this

Masemola, A. M., Mashishi, T. N., Khoury, G., Bredell, H., Paximadis, M., Mathebula, T., ... Allen, M. (2004). Novel and promiscuous CTL epitopes in conserved regions of Gag targeted by individuals with early subtype C HIV type 1 infection from Southern Africa. Journal of Immunology, 173(7), 4607-4617.

Novel and promiscuous CTL epitopes in conserved regions of Gag targeted by individuals with early subtype C HIV type 1 infection from Southern Africa. / Masemola, Agatha M.; Mashishi, Tumelo N.; Khoury, Greg; Bredell, Helba; Paximadis, Maria; Mathebula, Tiyani; Barkhan, Debra; Puren, Adrian; Vardas, Efthyia; Colvin, Mark; Zijenah, Lynn; Katzenstein, David; Musonda, Rosemary; Allen, Susan; Kumwenda, Newton; Taha, Taha E; Gray, Glenda; McIntyre, James; Karim, Salim Abdool; Sheppard, Haynes W.; Gray, Clive M.; Klautzman, Michelle; Kumwenda, Newton; Aquino, Victoria; Chirenje, Michael; Mbizo, Mike; Tobaiwa, Ocean; Mafhandu, Armstrong; Msweli, Dudu; Dlamini, Wendy; Ramjee, Gita; Karim, Quarraisha Abdool; Morris, Lynn; Taylor, Natasha; Williamson, Carolyn; Rademayer, Celia; Flores, Jorge; Cates, Ward; McNeil, Linda; Allen, Missie.

In: Journal of Immunology, Vol. 173, No. 7, 01.10.2004, p. 4607-4617.

Research output: Contribution to journalArticle

Masemola, AM, Mashishi, TN, Khoury, G, Bredell, H, Paximadis, M, Mathebula, T, Barkhan, D, Puren, A, Vardas, E, Colvin, M, Zijenah, L, Katzenstein, D, Musonda, R, Allen, S, Kumwenda, N, Taha, TE, Gray, G, McIntyre, J, Karim, SA, Sheppard, HW, Gray, CM, Klautzman, M, Kumwenda, N, Aquino, V, Chirenje, M, Mbizo, M, Tobaiwa, O, Mafhandu, A, Msweli, D, Dlamini, W, Ramjee, G, Karim, QA, Morris, L, Taylor, N, Williamson, C, Rademayer, C, Flores, J, Cates, W, McNeil, L & Allen, M 2004, 'Novel and promiscuous CTL epitopes in conserved regions of Gag targeted by individuals with early subtype C HIV type 1 infection from Southern Africa', Journal of Immunology, vol. 173, no. 7, pp. 4607-4617.
Masemola, Agatha M. ; Mashishi, Tumelo N. ; Khoury, Greg ; Bredell, Helba ; Paximadis, Maria ; Mathebula, Tiyani ; Barkhan, Debra ; Puren, Adrian ; Vardas, Efthyia ; Colvin, Mark ; Zijenah, Lynn ; Katzenstein, David ; Musonda, Rosemary ; Allen, Susan ; Kumwenda, Newton ; Taha, Taha E ; Gray, Glenda ; McIntyre, James ; Karim, Salim Abdool ; Sheppard, Haynes W. ; Gray, Clive M. ; Klautzman, Michelle ; Kumwenda, Newton ; Aquino, Victoria ; Chirenje, Michael ; Mbizo, Mike ; Tobaiwa, Ocean ; Mafhandu, Armstrong ; Msweli, Dudu ; Dlamini, Wendy ; Ramjee, Gita ; Karim, Quarraisha Abdool ; Morris, Lynn ; Taylor, Natasha ; Williamson, Carolyn ; Rademayer, Celia ; Flores, Jorge ; Cates, Ward ; McNeil, Linda ; Allen, Missie. / Novel and promiscuous CTL epitopes in conserved regions of Gag targeted by individuals with early subtype C HIV type 1 infection from Southern Africa. In: Journal of Immunology. 2004 ; Vol. 173, No. 7. pp. 4607-4617.
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title = "Novel and promiscuous CTL epitopes in conserved regions of Gag targeted by individuals with early subtype C HIV type 1 infection from Southern Africa",
abstract = "Characterization of optimal CTL epitopes in Gag can provide crucial information for evaluation of candidate vaccines in populations at the epicenter of the HIV-1 epidemic. We screened 38 individuals with recent subtype C HIV-1 infection using overlapping consensus C Gag peptides and hypothesized that unique HLA-restricting alleles in the southern African population would determine novel epitope identity. Seventy-four percent of individuals recognized at least one Gag peptide pool. Ten epitopic regions were identified across p17, p24, and p2p7p1p6, and greater than two-thirds of targeted regions were directed at: TGTEELRSLYN TVATLY (p17, 35{\%}); GPKEPFRDYVDRFFKTLRAEQATQDV (p24, 19{\%}); and RGGKLDKWEKIRLRPGGKKHYMLKHL (p17, 15{\%}). After alignment of these epitopic regions with consensus M and a consensus subtype C sequence from the cohort, it was evident that the regions targeted were highly conserved. Fine epitope mapping revealed that five of nine identified optimal Gag epitopes were novel: HLVWASREL, LVWASRELERF, LYNTVATLY, PFRDYVDRFF, and TLRAEQATQD, and were restricted by unique HLA-Cw*08, HLA-A*30/B*57, HLA-A*29/B*44, and HLA-Cw*03 alleles, respectively. Notably, three of the mapped epitopes were restricted by more than one HLA allele. Although these epitopes were novel and restricted by unique HLA, they overlapped or were embedded within previously described CTL epitopes from subtype B HIV-1 infection. These data, emphasize the promiscuous nature of epitope binding and support our hypothesis that HLA diversity between populations can shape line epitope identity, but may not represent a constraint for universal recognition of Gag in highly conserved domains.",
author = "Masemola, {Agatha M.} and Mashishi, {Tumelo N.} and Greg Khoury and Helba Bredell and Maria Paximadis and Tiyani Mathebula and Debra Barkhan and Adrian Puren and Efthyia Vardas and Mark Colvin and Lynn Zijenah and David Katzenstein and Rosemary Musonda and Susan Allen and Newton Kumwenda and Taha, {Taha E} and Glenda Gray and James McIntyre and Karim, {Salim Abdool} and Sheppard, {Haynes W.} and Gray, {Clive M.} and Michelle Klautzman and Newton Kumwenda and Victoria Aquino and Michael Chirenje and Mike Mbizo and Ocean Tobaiwa and Armstrong Mafhandu and Dudu Msweli and Wendy Dlamini and Gita Ramjee and Karim, {Quarraisha Abdool} and Lynn Morris and Natasha Taylor and Carolyn Williamson and Celia Rademayer and Jorge Flores and Ward Cates and Linda McNeil and Missie Allen",
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T1 - Novel and promiscuous CTL epitopes in conserved regions of Gag targeted by individuals with early subtype C HIV type 1 infection from Southern Africa

AU - Masemola, Agatha M.

AU - Mashishi, Tumelo N.

AU - Khoury, Greg

AU - Bredell, Helba

AU - Paximadis, Maria

AU - Mathebula, Tiyani

AU - Barkhan, Debra

AU - Puren, Adrian

AU - Vardas, Efthyia

AU - Colvin, Mark

AU - Zijenah, Lynn

AU - Katzenstein, David

AU - Musonda, Rosemary

AU - Allen, Susan

AU - Kumwenda, Newton

AU - Taha, Taha E

AU - Gray, Glenda

AU - McIntyre, James

AU - Karim, Salim Abdool

AU - Sheppard, Haynes W.

AU - Gray, Clive M.

AU - Klautzman, Michelle

AU - Kumwenda, Newton

AU - Aquino, Victoria

AU - Chirenje, Michael

AU - Mbizo, Mike

AU - Tobaiwa, Ocean

AU - Mafhandu, Armstrong

AU - Msweli, Dudu

AU - Dlamini, Wendy

AU - Ramjee, Gita

AU - Karim, Quarraisha Abdool

AU - Morris, Lynn

AU - Taylor, Natasha

AU - Williamson, Carolyn

AU - Rademayer, Celia

AU - Flores, Jorge

AU - Cates, Ward

AU - McNeil, Linda

AU - Allen, Missie

PY - 2004/10/1

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N2 - Characterization of optimal CTL epitopes in Gag can provide crucial information for evaluation of candidate vaccines in populations at the epicenter of the HIV-1 epidemic. We screened 38 individuals with recent subtype C HIV-1 infection using overlapping consensus C Gag peptides and hypothesized that unique HLA-restricting alleles in the southern African population would determine novel epitope identity. Seventy-four percent of individuals recognized at least one Gag peptide pool. Ten epitopic regions were identified across p17, p24, and p2p7p1p6, and greater than two-thirds of targeted regions were directed at: TGTEELRSLYN TVATLY (p17, 35%); GPKEPFRDYVDRFFKTLRAEQATQDV (p24, 19%); and RGGKLDKWEKIRLRPGGKKHYMLKHL (p17, 15%). After alignment of these epitopic regions with consensus M and a consensus subtype C sequence from the cohort, it was evident that the regions targeted were highly conserved. Fine epitope mapping revealed that five of nine identified optimal Gag epitopes were novel: HLVWASREL, LVWASRELERF, LYNTVATLY, PFRDYVDRFF, and TLRAEQATQD, and were restricted by unique HLA-Cw*08, HLA-A*30/B*57, HLA-A*29/B*44, and HLA-Cw*03 alleles, respectively. Notably, three of the mapped epitopes were restricted by more than one HLA allele. Although these epitopes were novel and restricted by unique HLA, they overlapped or were embedded within previously described CTL epitopes from subtype B HIV-1 infection. These data, emphasize the promiscuous nature of epitope binding and support our hypothesis that HLA diversity between populations can shape line epitope identity, but may not represent a constraint for universal recognition of Gag in highly conserved domains.

AB - Characterization of optimal CTL epitopes in Gag can provide crucial information for evaluation of candidate vaccines in populations at the epicenter of the HIV-1 epidemic. We screened 38 individuals with recent subtype C HIV-1 infection using overlapping consensus C Gag peptides and hypothesized that unique HLA-restricting alleles in the southern African population would determine novel epitope identity. Seventy-four percent of individuals recognized at least one Gag peptide pool. Ten epitopic regions were identified across p17, p24, and p2p7p1p6, and greater than two-thirds of targeted regions were directed at: TGTEELRSLYN TVATLY (p17, 35%); GPKEPFRDYVDRFFKTLRAEQATQDV (p24, 19%); and RGGKLDKWEKIRLRPGGKKHYMLKHL (p17, 15%). After alignment of these epitopic regions with consensus M and a consensus subtype C sequence from the cohort, it was evident that the regions targeted were highly conserved. Fine epitope mapping revealed that five of nine identified optimal Gag epitopes were novel: HLVWASREL, LVWASRELERF, LYNTVATLY, PFRDYVDRFF, and TLRAEQATQD, and were restricted by unique HLA-Cw*08, HLA-A*30/B*57, HLA-A*29/B*44, and HLA-Cw*03 alleles, respectively. Notably, three of the mapped epitopes were restricted by more than one HLA allele. Although these epitopes were novel and restricted by unique HLA, they overlapped or were embedded within previously described CTL epitopes from subtype B HIV-1 infection. These data, emphasize the promiscuous nature of epitope binding and support our hypothesis that HLA diversity between populations can shape line epitope identity, but may not represent a constraint for universal recognition of Gag in highly conserved domains.

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