Consruction of peptides encompassing multideterminant clusters of human immunodeficiency virus envelope to induce in vitro T cell responses in mice and humans of multiple MHC types

Jay A. Berzofsky, C. David Pendleton, Mario Clerici, Jeffrey Ahlers, Daniel R. Lucey, Scott D. Putney, Gene M. Shearer

Research output: Contribution to journalArticle

Abstract

To make synthetic peptide vaccines effective in a broad population of outbred humans, one would have to incorporate enough antigenic determinants to elicit recognition by T cells of most HLA types. We have previously defined multideterminant regions of the human immunodeficiency virus (HIV) envelope that include overlapping determinants seen by proliferating T cells of three or four haplotypes of mice. We have now tested the hypothesis that synthetic peptides encompassing such multideterminant regions will be recognized by T cells of multiple murine MHC types as well as by human T cells representing multiple HLA types. Six such peptides of 20-33 residues in length were prepared, and tested for their ability to stimulate T cells from mice of four distinct MHC types immunized with recombinant envelope protein rgp160, as well as from 42 HIV-infected humans of different HLA types. Results identify several such peptides that are broadly recognized by mice of four H-2 types and by 52-73% of infected humans who still retain 1L-2 productive responses to control recall antigens such as influenza A virus or tetanus toxoid. 86% of such infected donors tested against at least three peptides respond to at least one of the six peptides, and 77% of an additional group of seropositives respond to a mixture of the peptides. Moreover, the peptides can be used to immunize mice to elicit T cells reactive with the intact HIV envelope protein. These peptides therefore may be useful for both vaccine development in the broad human population, and diagnostic or prognostic use.

Original languageEnglish
Pages (from-to)876-884
Number of pages9
JournalJournal of Clinical Investigation
Volume88
Issue number3
Publication statusPublished - Sep 1991

Keywords

  • AIDS
  • Epitopes
  • HIV
  • HLA
  • T lymphocyte
  • Vaccine

ASJC Scopus subject areas

  • Medicine(all)

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