| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
,¶
* National Institute for Communicable Diseases, and
Perinatal HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa;
Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa;
HIV Vaccine and Prevention Trials Unit, Medical Research Council, and
¶
University of KwaZulu Natal, Durban, South Africa;
||
Department of Immunology, University of Zimbabwe, Harare, Zimbabwe;
#
Center for AIDS Research, Stanford University Medical Center, Palo Alto, CA 94305;
**
Zambia-University of Alabama at Birmingham HIV Research Project, Lusaka, Zambia;
Johns Hopkins Research Project, Blantyre, Malawi; and
*
California Department of Health Sciences, Richmond, CA 94804
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: TGTEELRSLYNTVATLY (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 fine epitope identity, but may not represent a constraint for universal recognition of Gag in highly conserved domains.
This article has been cited by other articles:
|
|
 |
|
  A. Maxmen Salim "Slim" Abdool Karim: Attacking AIDS in South Africa J. Exp. Med., October 26, 2009; 206(11): 2306 - 2307. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Abraha, I. L. Nankya, R. Gibson, K. Demers, D. M. Tebit, E. Johnston, D. Katzenstein, A. Siddiqui, C. Herrera, L. Fischetti, et al. CCR5- and CXCR4-Tropic Subtype C Human Immunodeficiency Virus Type 1 Isolates Have a Lower Level of Pathogenic Fitness than Other Dominant Group M Subtypes: Implications for the Epidemic J. Virol., June 1, 2009; 83(11): 5592 - 5605. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Gray, M. Mlotshwa, C. Riou, T. Mathebula, D. de Assis Rosa, T. Mashishi, C. Seoighe, N. Ngandu, F. van Loggerenberg, L. Morris, et al. Human Immunodeficiency Virus-Specific Gamma Interferon Enzyme-Linked Immunospot Assay Responses Targeting Specific Regions of the Proteome during Primary Subtype C Infection Are Poor Predictors of the Course of Viremia and Set Point J. Virol., January 1, 2009; 83(1): 470 - 478. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. K. Chege, E. G. Shephard, A. Meyers, J. van Harmelen, C. Williamson, A. Lynch, C. M. Gray, E. P. Rybicki, and A.-L. Williamson HIV-1 subtype C Pr55gag virus-like particle vaccine efficiently boosts baboons primed with a matched DNA vaccine J. Gen. Virol., September 1, 2008; 89(9): 2214 - 2227. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Perez, M. V. Larsen, R. Gustafsson, M. M. Norstrom, A. Atlas, D. F. Nixon, M. Nielsen, O. Lund, and A. C. Karlsson Broadly Immunogenic HLA Class I Supertype-Restricted Elite CTL Epitopes Recognized in a Diverse Population Infected with Different HIV-1 Subtypes J. Immunol., April 1, 2008; 180(7): 5092 - 5100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Turk, M. M. Gherardi, N. Laufer, M. Saracco, R. Luzzi, J. H. Cox, P. Cahn, and H. Salomon Magnitude, Breadth, and Functional Profile of T-Cell Responses during Human Immunodeficiency Virus Primary Infection with B and BF Viral Variants J. Virol., March 15, 2008; 82(6): 2853 - 2866. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. O. Peters, M. G. Mendoza, R. E. Capina, M. Luo, X. Mao, M. Gubbins, N. J. D. Nagelkerke, I. MacArthur, B. B. Sheardown, J. Kimani, et al. An Integrative Bioinformatic Approach for Studying Escape Mutations in Human Immunodeficiency Virus Type 1 gag in the Pumwani Sex Worker Cohort J. Virol., February 15, 2008; 82(4): 1980 - 1992. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Nakagawa, K. H. Kim, T. M. Gillam, and A.-B. Moscicki HLA Class I Binding Promiscuity of the CD8 T-Cell Epitopes of Human Papillomavirus Type 16 E6 Protein J. Virol., February 1, 2007; 81(3): 1412 - 1423. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Li, A. D. Gladden, M. Altfeld, J. M. Kaldor, D. A. Cooper, A. D. Kelleher, and T. M. Allen Rapid Reversion of Sequence Polymorphisms Dominates Early Human Immunodeficiency Virus Type 1 Evolution J. Virol., January 1, 2007; 81(1): 193 - 201. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Honeyborne, A. Rathod, R. Buchli, D. Ramduth, E. Moodley, P. Rathnavalu, S. Chetty, C. Day, C. Brander, W. Hildebrand, et al. Motif Inference Reveals Optimal CTL Epitopes Presented by HLA Class I Alleles Highly Prevalent in Southern Africa. J. Immunol., April 15, 2006; 176(8): 4699 - 4705. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Zuniga, A. Lucchetti, P. Galvan, S. Sanchez, C. Sanchez, A. Hernandez, H. Sanchez, N. Frahm, C. H. Linde, H. S. Hewitt, et al. Relative Dominance of Gag p24-Specific Cytotoxic T Lymphocytes Is Associated with Human Immunodeficiency Virus Control J. Virol., March 15, 2006; 80(6): 3122 - 3125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Geels, S. A. Dubey, K. Anderson, E. Baan, M. Bakker, G. Pollakis, W. A. Paxton, J. W. Shiver, and J. Goudsmit Broad Cross-Clade T-Cell Responses to Gag in Individuals Infected with Human Immunodeficiency Virus Type 1 Non-B Clades (A to G): Importance of HLA Anchor Residue Conservation J. Virol., September 1, 2005; 79(17): 11247 - 11258. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
