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

Abstract 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 n...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2007-04, Vol.361 (1), p.34-44
Main Authors: Boritz, Eli, Rapaport, Eric L, Campbell, Thomas B, Koeppe, John R, Wilson, Cara C
Format: Article
Language:English
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
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Summary:Abstract 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.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2006.10.040