CD4 + T cell targeting of human immunodeficiency virus type 1 (HIV-1) peptide sequences present in vivo during chronic, progressive HIV-1 disease

• Published in: Virology (New York, N.Y.) Vol. 361; no. 1; pp. 34 - 44
• Main Authors: Boritz, Eli, Rapaport, Eric L., Campbell, Thomas B., Koeppe, John R., Wilson, Cara C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.04.2007
• Subjects: Amino Acid Sequence; CD4 + T cells; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes - immunology; Chronic Disease; Disease Progression; Epitopes; Epitopes, T-Lymphocyte - genetics; Fluorides; Gag protein; HIV Core Protein p24 - genetics; HIV Core Protein p24 - immunology; HIV Infections - diagnosis; HIV Infections - immunology; HIV Infections - virology; HIV-1 - genetics; HIV-1 - immunology; HIV-1 - isolation & purification; Human immunodeficiency virus type 1; Humans; Infectious Disease; Methacrylates; Molecular Sequence Data; Mutations; Phylogeny; Polyurethanes; RNA, Viral; T-Cell Antigen Receptor Specificity; Viral Load; Mutations; Human immunodeficiency virus type 1; CD4 + T cells; Epitopes; Gag protein
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2006.10.040

We previously detected HIV-1 Gag-specific CD4 + T cells recognizing reference strain viral epitopes in subjects with progressive, chronic infection. To test whether these CD4 + T cells persist in vivo by failing to recognize autologous HIV-1 epitopes, we compared autologous plasma HIV-1 p24 nucleotide sequences with targeted HXB.2 strain Gag p24 CD4 + T cell epitopes in nine chronically infected, untreated subjects. In five responding subjects, 10 of 26 HXB.2 strain p24 peptides targeted by CD4 + T cells exactly matched autologous plasma viral sequences. Four subjects with plasma viral loads > 100,000 copies/mL had no measurable p24-specific CD4 + T cell responses despite carrying HIV-1 strains that matched HXB.2 sequences at predicted epitopes. These results show that HIV-1-specific CD4 + T cells can persist in chronic HIV-1 infection despite recognition of epitopes present in vivo. However, with high-level in vivo HIV-1 replication, CD4 + T cells targeting autologous HIV-1 may be non-responsive or absent.