Broadly Immunogenic HLA Class I Supertype-Restricted Elite CTL Epitopes Recognized in a Diverse Population Infected with Different HIV-1 Subtypes

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 predicte...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2008-04, Vol.180 (7), p.5092-5100
Main Authors: Perez, Carina L, Larsen, Mette V, Gustafsson, Rasmus, Norstrom, Melissa M, Atlas, Ann, Nixon, Douglas F, Nielsen, Morten, Lund, Ole, Karlsson, Annika C
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Epitopes, T-Lymphocyte - chemistry
Epitopes, T-Lymphocyte - immunology
Histocompatibility Antigens Class I - immunology
HIV Infections - classification
HIV Infections - epidemiology
HIV Infections - immunology
HIV-1 - classification
HIV-1 - immunology
Human immunodeficiency virus 1
Humans
Medicin och hälsovetenskap
Molecular Sequence Data
T-Lymphocytes, Cytotoxic - immunology
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.180.7.5092