Persistent HIV-1-specific CTL clonal expansion despite high viral burden post in utero HIV-1 infection
Department of Pediatrics
Medical Subject Headings
Child, Preschool; Clone Cells; Cytotoxicity Tests, Immunologic; Epitopes, T-Lymphocyte; Female; Gene Products, gag; HIV Infections; HIV-1; Humans; Infant; Lymphocyte Count; Pregnancy; Pregnancy Complications, Infectious; Puerperal Infection; Stem Cells; T-Lymphocytes, Cytotoxic; *Viral Load; Virus Latency; Virus Replication
Immunology and Infectious Disease | Pediatrics
To address the issue of clonal exhaustion in humans, we monitored HLA class I-restricted, epitope-specific CTL responses in an in utero HIV-1-infected infant from 3 mo through 5 years of age. Serial functional CTL precursor assays demonstrated persistent, vigorous, and broadly directed HIV-1 specific CTL activity with a dominant response against an epitope in HIV-1 Gag-p17 (SLYNTVATL, aa 77-85). A clonal CTL response directed against the immunodominant, HLA-A*0201-restricted epitope was found to persist over the entire observation period, as shown by TCR analysis of cDNA libraries generated from PBMC. The analysis of autologous viral sequences did not reveal any escape mutations within the targeted epitope, and viral load measurement indicated ongoing viral replication. Furthermore, inhibition of viral replication assays indicated that the epitope was properly processed from autologous viral protein. These data demonstrate that persistent exposure to high levels of viral Ag does not necessarily lead to clonal exhaustion and that epitope-specific clonal CTL responses induced within the first weeks of life can persist for years without inducing detectable viral escape variants.
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Citation: J Immunol. 1999 Apr 15;162(8):4796-800.