TY - JOUR
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
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
Y1 - 2004/10/1
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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U2 - 10.4049/jimmunol.173.7.4607
DO - 10.4049/jimmunol.173.7.4607
M3 - Article
C2 - 15383595
AN - SCOPUS:4644299613
SN - 0022-1767
VL - 173
SP - 4607
EP - 4617
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -