Detection of Human Immunodeficiency Virus Type 1 Envelope Peptide- Stimulated T-helper Cell Responses and Variations in the Corresponding Regions of Viral Isolates among Vertically Infected Children

Abstract

Although human immunodeficiency virus type 1 (HIV-1) specific CD4 T-helper cells are vital in mediating antiviral defence, little is known concerning the influence of HIV-1 antigenic variation on CD4 T-cell responses. In this study, the amino acid sequences of 5 synthetic HIV-1 envelope peptides used for in vitro stimulation (T2, P18 MN, P18 IIIB, T1 and TH4.1) were compared to the corresponding amino acid sequences of the gp 160 region of viruses isolated from HIV-1 infected children to determine whether variation in the envelope region of HIV-1 was associated with the ability to detect Env-specifice T-helper cell responses. Although the T2 region appeared to offer some evidence as to the role antigenic variation may have played in class II-restricted CD4 T-cell responses between those children who showed a detectable Env-stimulated T-helper cell response and those who did not, the other regions studied showed no evidence of being more conserved among those children who showed detectable responses. The combined amino acid variation across the specific peptide reions studied was not associated with peripheral levels of HIV-1, nor did the degree of amino acid variation dictate the clinical category into which the children had been classified, although there was a tendency towards HIV-1 isolates from the younger children showing a greater degree of amino acid variation than isolates from the older children. These results suggest that HIV-1 specific CD4 responses may be somewhat tolerant of viral variation, although further studies are required to fully elucidate the effect of antigenic variation on immune recognition.

Frequent associations between CTL and T-Helper epitopes in HIV-1 genomes and implications for multi-epitope vaccine designs

“…Furthermore, different immune responses can target the same regions of viral peptides. For example, V3-loop peptides of the Env gene can be presented by both class I and class II major histocompatibility complex (MHC) molecules and can be recognized by both Cytotoxic T-Lymphocytes (CTLs) and T-Helper cells (Th), as well as by neutralizing antibodies (Ab) (e.g., [ 16 - 18 ]). Likewise, a highly conserved region in the Gag gene (287-309 amino acid residues in p24) has been shown to interact with CTL, as well as B and T-Helper cells [ 19 ].…”

Susceptibility and adaptation to human TRIM5α alleles at positive selected sites in HIV-1 capsid

“…On the other hand, immune response and drugs impose positive selection on HIV-1 leading to the emergence of viral escape mutants Telenti, 2005). HIV-1 escape mutants are generated in response to adaptive immune defense mediated by antibodies, cytotoxic T lymphocytes (CTL) and to a lesser extent by T helper lymphocytes (Goulder and Watkins, 2008;Henn et al, 2012;Meddows-Taylor et al, 2004;Paul and Piontkivska, 2010;Richman et al, 2003;Wei et al, 2003). Recently, killer inhibitory receptors (KIR) from natural killer cells were also shown to exert pressure on HIV-1 and to induce escape mutants (Alter et al, 2011).…”