Role of flanking variable sequences in antigenicity of consensus regions of HIV gp120 for recognition by specific human T helper clones

Abstract

Human T helper cells can discriminate among strain variants of HIV gp120 because of T cell clones recognizing non-conserved regions, as demonstrated with T cells from HIV-infected individuals and vaccinated volunteers and with primary T cell lines and clones obtained by in vitro immunization. To obtain a better definition of cross-reactions among T cell determinants within HIV gp120 variants, we used a panel of analog peptides within residues 236-251 from the BRU, MN, SF2 and RF strain sequences to induce primary human T cell lines and clones. Different patterns of response were obtained using each of the analog peptides, although they all share the consensus sequence 246-251. Clones recognizing this sequence were generated by priming with the BRU and RF analog peptides, but not with the SF2 analog peptide. SF2 did not induce any 242-245-specific clones, but only T cells recognizing the 236-240 sequence. A preferential response to residues 236-240 was obtained by priming with the BRU and SF2 peptides, but not with the MN and RF peptides. These results suggest that although the analog peptides exhibit a high degree of homology and share a consensus of the C-terminal sequence (246-251), the T cell response to the conserved sequence 246-251 is controlled by flanking sequences. Therefore the presence of a shared sequence per se does not imply in vitro expansion of clones with that fine specificity, even though such clones are available within the naive repertoire and can be triggered by an analog peptide.

Human T helper cells specific for HIV reverse transcriptase: possible role in intrastructural help for HIV envelope‐specific antibodies

“…Clonal heterogeneity of p66-specific T cells is remarkable, considering that the Th response to p66 focuses on limited regions of the Ag, as shown with gp120 [17]. Yet clonal diversity of T cells focusing on a limited region has also been observed with mouse Th clones specific for lysozyme [48].…”

“…T cell lines were generated from individuals not immune to HIV as detailed [17] by stimulation with antigen-pulsed APC and IL-2-driven expansion. Bulk lines were cloned by limiting dilution at 0.5 cells/well [23].…”

Human T leukaemia virus type 1 (HTLV‐1) specific T‐helper cell response: clonal fluctuations and repertoire heterogeneity

“…More details on these lines have been given in a previous report (Manca et al, 1995c). As we have observed with other retroviral antigens (Manca et al, 1991(Manca et al, , 1993(Manca et al, , 1995a, the in vitro Th cell response of naive individuals to HTLV-1 env focuses on limited (immunodominant) regions of the protein, identified when overlapping peptides are used to screen the lines for fine specificity. Certain lines respond to protein antigens, but not to any synthetic peptides.…”

Immunization with Human Immunodeficiency Virus Type 1 rgp120W61Din QS21/MPL Adjuvant Primes T Cell Proliferation and C‐C Chemokine Production to Multiple Epitopes within Variable and Conserved Domains of gp120W61D

“…However, peptide B2, which encompasses the entire sequence of the envT2 peptide, failed to induce proliferation in any of the TCL, suggesting that the epitope recognized is dependent on flanking residues within the B1 peptide. The importance of amino acid residues flanking epitopes has been previously reported [33].…”