CROSS-REACTIVE T-CELL PROLIFERATIVE RESPONSES TO V3 PEPTIDES CORRESPONDING TO DIFFERENT GEOGRAPHICAL HIV-1 ISOLATES IN HIV-SEROPOSITIVE INDIVIDUALS

We have investigated the proliferative response of peripheral blood mo nonuclear cells from individuals infected with human immunodeficiency virus type 1 (HIV-I) to synthetic peptides from the third variable loo p region (V3) in the envelope protein gp120. We tested a total of 14 p eptides, corresponding to 14 HIV-1 isolates belonging to four geograph ical locations (clades U, A, B, and D). Although differences in relati ve level of responses exist between individual peptides and patients, the proliferation in response to all 14 V3 peptides was significantly greater than that to unrelated control peptides. Additionally, we obse rved that proliferative responses of blood cells from the 10 HIV-serop ositive individuals studied from the clade B region to peptides from w ithin clades U, A, B, and D were not significantly different, indicati ng the cross-reactive nature of the V3-specific cell-mediated immune r esponses. Even though the majority of patients also exhibited antibody responses against several V3 peptides, serum samples from 50% of clad e B patients exhibited antibody cross-reactivity, while proliferative responses to V3 peptides from more than one clade were observed in 80% of patients. Importantly, in two patients, decreased CD4(+) cell numb ers, an important surrogate marker of disease progression, significant ly correlated with loss of V3 peptide-specific proliferative responses but not-antibody responses. These results have important implications toward evaluating the utility of V3 peptides for designing therapeuti c and/or vaccine reagents against HIV-1.