Studies on V3-specific cross-reactive T-cell responses in chimpanzees chronically infected with HIV-1IIIB.

OBJECTIVE AND DESIGN

In this study we used synthetic peptides corresponding to the third variable region (V3) in the envelope protein gp120 of 14 different HIV-1 strains, and tested whether V3-specific T-cell responses are HIV-1 strain-specific or broadly cross-reactive in nine chimpanzees chronically infected with HIV-1IIIB.

METHODS

Peripheral blood mononuclear cells isolated from nine HIV-infected chimpanzees and two uninfected controls were tested, by the [3H]-thymidine incorporation assay, for proliferative responses against phytohemagglutinin, control peptide and V3-loop peptides corresponding to 14 different HIV-1 strains. Serum samples collected from the chimpanzees were analyzed by enzyme-linked immunosorbent assay for antibodies against the V3 peptides.

RESULTS

Chimpanzees 100, 139 and 175 exhibited high level of proliferative response directed against the cognate V3 peptide from HIV-1IIIB and also showed cross-reactivity to V3 peptides from 13, seven and 13 of 13 other HIV-1 strains, respectively. Additionally, five out of nine chimpanzees showed cross-reactive proliferative responses to V3 peptides from at least eight different HIV-1 strains, while significant proliferation to V3 peptides from two or more HIV-1 strains was observed in seven out of nine chimpanzees. On the other hand, four out of nine chimpanzees showed antibody response directed against the cognate V3 peptide from HIV-1IIIB, and serum from only one chimpanzee (100) showed cross-reactive antibody to six different V3 peptides.

CONCLUSIONS

Overall, these studies in chimpanzees chronically infected with HIV-1IIIB indicate that with respect to the immunodominant V3 region, the virus-induced T-cell immunity is directed against a broad spectrum of HIV-1 strains.