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69 Gag-Specific CD8+ T-Lymphocyte Immunodominant Epitopes in HIV-1-Infected Individuals from Democratic Republic of Congo
N. Lubaki*1, M. Kashamuka2, L. Musey3, L. Atibu2, B. Milangu2, N. Nzila2, L. Cheng4, H. Huiming5, S. Keating1, L. Carruth1, T. Quinn1, and R. Bollinger1
1Johns Hopkins Univ., Baltimore, MD, USA; 2Projet SIDA, Kinshasa, RDC; 3Univ. of Washington, Seattle, USA; 4CDC, Atlanta, GA, USA; and 5Emory Univ., Atlanta, GA, USA
Background: Induction of CD8+ T-cell responses may be important for candidate HIV-1 vaccines. CD8+ T-cell epitopes identified thus far have been primarily from clade-B-infected individuals. Because most HIV-1-infections are with non-B viruses, characterization of the CD8+ T-cell epitopes in other populations may be important for the design of HIV-1 vaccines.
Methods: Using the ELISPOT method for detection of IFN-gamma producing CD8+ T lymphocytes, peripheral blood mononuclear cells (PBMC) from 14 HIV-infected individuals from Kinshasa, Democratic Republic of Congo, were analyzed for the presence of T-lymphocyte recognition of pools of overlapping HIV-1 subtype A gag peptides. Information on HIV-1 subtype infecting participants was limited to DNA sequencing of the env C2V3 region.
Results: PBMC from 7 (50%) of 14 HIV-1-infected participants demonstrated T-cell recognition of HIV-1 subtype A gag peptides. Five subjects responded to at least 2 gag peptides. One subject recognized 5 different gag epitopes. No statistically significant differences in HIV viral load were observed between gag-responders and nonresponders. Most of the epitopes from responders infected with HIV-1 A, C, and H, were located in relatively well-conserved regions within the p17 and p24 region of the gag protein. Seven of the 8 epitopes were previously described from HIV-1 subtype B-infected individuals. In addition, recognition of a novel HLA-B81 restricted epitope (71GTEELRSLYNTVATLYCVHQ90) was identified.
Conclusions: HIV-1-infected individuals from DRC primarily recognize conserved T-lymphocyte epitopes from immunologic hot spots within HIV-1 gag. However, a novel HLA-B81-restricted epitope was also identified. Further characterization of T-lymphocyte epitopes from regions with diverse HIV-1 subtypes and populations with diverse HLA-alleles may be important for selection and development of HIV-1 vaccine candidates for these regions of the world in most need of a vaccine.
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