STUDIES ON V3-SPECIFIC CROSS-REACTIVE T-CELL RESPONSES IN CHIMPANZEESCHRONICALLY INFECTED WITH HIV-1(IIIB)

Objective and design: In this study we used synthetic peptides corresp onding 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-1(IIIB). Methods: Peripheral blood mononuclear cells isolated from nine HIV-infected chimpanzees a nd two uninfected controls were tested, by the [H-3]-thymidine incorpo ration 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 pe ptides. Results: Chimpanzees 100, 139 and 175 exhibited high level of proliferative response directed against the cognate V3 peptide from HI V-1(IIIB) and also showed cross-reactivity to V3 peptides from 13, sev en 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 sign ificant proliferation to V3 peptides from two or more HIV-1 strains wa s observed in seven out of nine chimpanzees. On the other hand, four o ut of nine chimpanzees showed antibody response directed against the c ognate V3 peptide from HIV-1(IIIB), and serum from only one chimpanzee (100) showed cross-reactive antibody to six different V3 peptides. Co nclusions: Overall, these studies in chimpanzees chronically infected with HIV-1(IIIB) indicate that with respect to the immunodominant V3 r egion, the virus-induced T-cell immunity is directed against a broad s pectrum of HIV-1 strains.