Definition of an immunodominant T cell epitope contained in the envelope gp41 sequence of HIV-1

Abstract

SUMMARYThe majority of the immunodominant amino acid sequences of HIV-I that have been characterized to date are coded for by hypervariable gene sequences. These variable sequences are however interspersed with sequences that are highly conserved between HIV striiins. Inimunogenic viral products with amino acid sequences that vary minimally between strains, and that consistently elicit both humoral and cellular immune responses, may be ideal for inclusion in a subunit vaccine. We studied HiV-seronegative and HIV-infected persons, classified as asymptomatic (AS), ARC or AIDS, initially, we assessed the cellular immune status of each subject from results of T eel! phenotypc analyses, assays for serum levels of surrogate markers of disease progression, and responses to mitogens and recall antigen. In addition, we tested whether three short synthetic peptides derived from the conserved sequences of the envelope gp 120 (aa 262-284) and gp41 (aa 579-601), and core p 17 (aa 106-125) regions of the HTLV-I MB isolate, could elicit B cell as well as T cell responses in HlV-infected subjects. Only the gp41-derived sequence was immunogenic at both B and Tcell levels. To further characterize the gp4l epitope. we used a series of overlapping synthetic peptides derived from aeonserved region of the envelope gp41 (aa 572-613). We thus identified an immunodominant 12-mer peptide sequence. gp41 {8K«ia 593-604).. which consistently elicited both T cell blastogenic and Bceil (antibody) responses in AS HIV-seropositive individuals but not in ARC and AIDS patients. Linear regression analysis showed that in AS persons [here was a strong positive correlation (/'<0()0()5) between the absolute CD8 * Teell numbers and the magnitude of blastogenic responses to thegp41!81(aa 593 604). Furthermore, those AS subjeets with T cells that proliferated in response to this gp41 analogue also had significantly greater serum levels of antibody to the same short peptide sequence than symptomatic ARC and AIDS patients. These results suggest that cellular responses to ihe immunodominant and highly conserved envelope sequences of HIV-1, associated with increased CDS' T cells, may be important in the pathogenesis of HIV disease.

Heterogeneous effects of exogenous IL-2 on HIV-specific cell-mediated immunity (CMI)

“…Immunodominant HIV gp4l analogues that were used to Furthermore, our results suggest that during the early and induce blastogenesis of HIV-specific T lymphocytes were genasymptomatic stage of HIV-mediated disease, there appeared to erated as described earlier [23,26]. An immunodominant HIV be a net deficiency of CD4+ T cell-derived endogenous IL-2 that analog (gp4l amino acids 593-604), derived from a highly may be required to maintain the highly activated anti-viral conserved envelope gp4l region of the HTLV-IIIB strain of CD8+ cells, and thus curtail productive infection.…”

“…This immunodominant syn-PATIENTS AND METHODS thetic peptide sequence is referred to as gp4l{8}. T cell phenotype analysis Results are expressed as stimulation indices, and proliferation Quality control measures were rigorously adhered to throughoccurred only if SI > 2-5 [23]. All tests were performed in out the study.…”

“…trypan blue exclusion). Bitmaps were continually adjusted frequency in a population of HIV-infected persons with diverse to encircle the majority of either stimulated or unstimulated MHC haplotypes [23]. Using this well defined in vitro model lymphocytes.…”

“…In the lead-up to the experiments designed to measure prolifermononuclear cells (PBMC) was analysed using dual immunoation of unstimulated PBMC in culture with exogenous rIL-2 fluorescence and flow cytometry, as described previously [23].…”

The Breadth of Expandable Memory CD8 + T Cells Inversely Correlates with Residual Viral Loads in HIV Elite Controllers

“…Our analysis focused on memory responses to three HIV proteins: Gag, Nef, and Env. We chose these three HIV proteins for the following reasons: (i) T cell responses directed to the HIV Gag protein have consistently been associated with lower-level viremia (17,(32)(33)(34)(35); (ii) Nef responses are immunodominant early during acute HIV infection and may be involved in the initial control of viremia, and therefore, their persistence may be relevant to long-term viral control (36)(37)(38)(39); and (iii) responses targeting the Env region have been shown to be important for both T cell and B cell immune responses (40)(41)(42), and the breadth of Env-specific responses has been positively associated with viral load (17,43). Thus, elucidating the role of long-lived responses to these HIV proteins may be relevant for vaccines.…”