CD4+ T cell targeting of human immunodeficiency virus type 1 (HIV-1) peptide sequences present in vivo during chronic, progressive HIV-1 disease.
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.
Boritz
Eli
E
Department of Immunology, University of Colorado Health Sciences Center, Denver, CO, USA. eboritz1@jhmi.edu
Rapaport
Eric L
EL
Campbell
Thomas B
TB
Koeppe
John R
JR
Wilson
Cara C
CC
D000595:Amino Acid Sequence; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D018450:Disease Progression; D018984:Epitopes, T-Lymphocyte / Q000235:genetics; D005459:Fluorides; D016655:HIV Core Protein p24 / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000175:diagnosis / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008689:Methacrylates; D008969:Molecular Sequence Data; D010802:Phylogeny; D011140:Polyurethanes; D012367:RNA, Viral; D037182:T-Cell Antigen Receptor Specificity; D019562:Viral Load
D018984:Epitopes, T-Lymphocyte; D016655:HIV Core Protein p24; D008689:Methacrylates; D011140:Polyurethanes; D012367:RNA, Viral; C091935:Sequence (bonding agent); D005459:Fluorides