COMPREHENSIVE T-CELL EPITOPE MAPPING OF HIV-1 ENV ANTIGENS REVEALS MANY AREAS RECOGNIZED BY HIV-1-SEROPOSITIVE AND BY LOW-RISK HIV-1-SERONEGATIVE INDIVIDUALS

Peripheral blood mononuclear cells from 12 asymptomatic human immunode ficiency virus (HIV)-1-seropositive and nine HIV-1-seronegative donors were screened for proliferative T-lymphocyte responses to peptides de rived from a consensus sequence of the HIV-1 env gene products from 25 HIV-1 isolates. Two hundred seventy-eight overlapping 17mer peptides, incremented by three residues each, were pooled into groups, each con taining eight sequential peptides, for use in proliferation tests. Thi rty-eight additional peptides containing variant amino acid residues a lso were tested. Proliferation data were analyzed using an algorithm t hat reduced subjective bias and estimated the responding cell frequenc ies. Peripheral blood mononuclear cells from a majority of donors, reg ardless of HIV-1 status, recognized peptides within two pools derived from the gp120 sequence and peptides from one pool in gp41. Pool 25 pe ptides from gp41 (centered around residue 600 of the gp160 consensus s equence) were recognized most frequently. The observed inability to di fferentiate between responses of HIV-1-seropositive and HIV-1-seronega tive individuals implies either a lack of HIV-1 disease-related immuno dominant env epitopes or functional abrogation of HIV-1 env-specific T -helper lymphocyte responses soon after infection. The observed prolif eration of T lymphocytes from noninfected, low-risk individuals questi ons the origin of the responses to HIV-1 env-derived peptides and sugg est that preexisting, cross-reactive immunity could influence response s to HIV-1.