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

S. J.D. Bell, D. A. Cooper, B. E. Kemp, R. R. Doherty, R. Penny

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Abstract

The 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 strains. Immunogenic 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 cell phenotype 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 HIV‐infected subjects. Only the gp41‐derived sequence was immunogenic at both B and T cell levels. To further characterize the gp41 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) (aa 593–604), which consistently elicited both T cell blastogenic and B cell (antibody) responses in AS HIV‐seropositive individuals but not in ARC and AIDS patients. Linear regression analysis showed that in AS persons there was a strong positive correlation (P<0·0005) between the absolute CD8* T cell numbers and the magnitude of blastogenic responses to the gp41(8)(aa 593–604). Furthermore, those AS subjects 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 the immunodominant and highly conserved envelope sequences of HIV‐1, associated with increased CDS+ T cells, may be important in the pathogenesis of HIV disease.

Original languageEnglish
Pages (from-to)37-45
Number of pages9
JournalClinical & Experimental Immunology
Volume87
Issue number1
DOIs
Publication statusPublished - 1 Jan 1992
Externally publishedYes

Keywords

  • B cell epitopes
  • HIV conserved sequence
  • synthetic peptide
  • T cell epitopes

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