Broadly Immunogenic HLA Class I Supertype-Restricted Elite CTL Epitopes Recognized in a Diverse Population Infected with Different HIV-1 Subtypes
- 1 April 2008
- journal article
- Published by Oxford University Press (OUP) in The Journal of Immunology
- Vol. 180 (7) , 5092-5100
- https://doi.org/10.4049/jimmunol.180.7.5092
Abstract
The genetic variations of the HIV-1 virus and its human host constitute major obstacles for obtaining potent HIV-1-specific CTL responses in individuals of diverse ethnic backgrounds infected with different HIV-1 variants. In this study, we developed and used a novel algorithm to select 184 predicted epitopes representing seven different HLA class I supertypes that together constitute a broad coverage of the different HIV-1 strains as well as the human HLA alleles. Of the tested 184 HLA class I-restricted epitopes, 114 were recognized by at least one study subject, and 45 were novel epitopes, not previously described in the HIV-1 immunology database. In addition, we identified 21 “elite” epitopes that induced CTL responses in at least 4 of the 31 patients. A majority (27 of 31) of the study population recognized one or more of these highly immunogenic epitopes. We also found a limited set of 9 epitopes that together induced HIV-1-specific CTL responses in all HIV-1-responsive patients in this study. Our results have important implications for the validation of potent CTL responses and show that the goal for a vaccine candidate in inducing broadly reactive CTL immune responses is attainable.Keywords
This publication has 53 references indexed in Scilit:
- Sequential Broadening of CTL Responses in Early HIV-1 Infection Is Associated with Viral EscapePLOS ONE, 2007
- Combined single‐clade candidate HIV‐1 vaccines induce T cell responses limited by multiple forms of in vivo immune interferenceEuropean Journal of Immunology, 2007
- HIV-1 Epitope-Specific CD8+ T Cell Responses Strongly Associated with Delayed Disease Progression Cross-Recognize Epitope Variants EfficientlyThe Journal of Immunology, 2006
- An integrative approach to CTL epitope prediction: A combined algorithm integrating MHC class I binding, TAP transport efficiency, and proteasomal cleavage predictionsEuropean Journal of Immunology, 2005
- Novel and Promiscuous CTL Epitopes in Conserved Regions of Gag Targeted by Individuals with Early Subtype C HIV Type 1 Infection from Southern AfricaThe Journal of Immunology, 2004
- Immunologic and virologic evolution during periods of intermittent and persistent low-level viremiaAIDS, 2004
- Definition of supertypes for HLA molecules using clustering of specificity matricesImmunogenetics, 2004
- Nine major HLA class I supertypes account for the vast preponderance of HLA-A and -B polymorphismImmunogenetics, 1999
- Dramatic Rise in Plasma Viremia after CD8+ T Cell Depletion in Simian Immunodeficiency Virus–infected MacaquesThe Journal of Experimental Medicine, 1999
- Human histocompatibility leukocyte antigen-binding supermotifs predict broadly cross-reactive cytotoxic T lymphocyte responses in patients with acute hepatitis.Journal of Clinical Investigation, 1997