Cytolytic T Lymphocytes (CTLs) from HIV-1 Subtype C–Infected Indian Patients Recognize CTL Epitopes from a Conserved Immunodominant Region of HIV-1 Gag and Nef

National AIDS Research Institute, Bhosari, Pune, India.
The Journal of Infectious Diseases (Impact Factor: 6). 10/2005; 192(5):749-59. DOI: 10.1086/432547
Source: PubMed


Analysis of the human immunodeficiency virus type 1 (HIV-1) cytolytic T lymphocyte (CTL) epitopes recognized by the targeted population is critical for HIV-1 vaccine design. Peripheral blood mononuclear cells from 47 Indian subjects at different stages of HIV-1 infection were tested for HIV-1 Gag-, Nef-, and Env-specific T cell responses by interferon (IFN)- gamma enzyme-linked immunospot (ELISPOT) assay, using pools of overlapping peptides. The Gag and Nef antigens were targeted by 83% and 36% of responders. Five immunodominant regions, 4 in Gag and 1 in Nef, were identified in the study; these regions are conserved across clades, including the African subtype C clade. Three antigenic regions were also found to be recognized by CTLs of the study participants. These regions were not identified as immunodominant regions in studies performed in Africa, which highlights the importance of differential clustering of responses within HIV-1 subtype C. Twenty-six putative epitopes--15 Gag (10 in p24 and 5 in p17), 10 Nef, and 1 Env (gp 41)--were predicted using a combination of peptide matrix ELISPOT assay and CTL epitope-prediction software. Ninety percent of the predicted epitopes were clustered in the conserved immunodominant regions of the Gag and Nef antigens. Of 26 predicted epitopes, 8 were promiscuous, 3 of which were highly conserved across clades. Three Gag and 4 Nef epitopes were novel. The identification of conserved epitopes will be important in the planning of an HIV-1 vaccine strategy for subtype C-affected regions.

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    • "Our data showed that the second half of p24 was the most immunodominant regions, followed by the first half of p17 regions. This finding is consistent with previous reports [13], [15], [27]. We were concerned that the compatibility between OLP sequences and circulating Gag sequences may vary depending on the conservativeness and influence on the pattern of Gag CTL responses. "
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    • "However the presence and the intensity of CTL responses in chronic HIV infection did not show any correlation with the indicators of disease progression, CD4 count or plasma viral load. Thakar et al (Thakar et al 2005) demonstrated that the patients infected with HIV-1 C from India recognize the antigenic determinants from the same segments of Gag and Nef proteins that are recognized by the HIV-1 subtype C infected patients from South Africa and Botswana. This observation has implications in vaccine "
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