Persistent HIV-1-specific CTL clonal expansion despite high viral burden post in utero HIV-1 infection

摘要: To address the issue of clonal exhaustion in humans, we monitored HLA class I-restricted, epitope-specific CTL responses an utero HIV-1-infected infant from 3 mo through 5 years age. Serial functional precursor assays demonstrated persistent, vigorous, and broadly directed HIV-1 specific activity with a dominant response against epitope Gag-p17 (SLYNTVATL, aa 77–85). A immunodominant, HLA-A*0201-restricted was found to persist over entire observation period, as shown by TCR analysis cDNA libraries generated PBMC. The autologous viral sequences did not reveal any escape mutations within targeted epitope, load measurement indicated ongoing replication. Furthermore, inhibition replication that properly processed protein. These data demonstrate persistent exposure high levels Ag does necessarily lead induced first weeks life can for without inducing detectable variants.