Long-term culture and fine specificity of human cytotoxic T-lymphocyte clones reactive with human immunodeficiency virus type 1

B. D. Walker, C. Flexner, K. Birch-Limberger, L. Fisher, T. J. Paradis, A. Aldovini, R. Young, B. Moss, R. T. Schooley

Research output: Contribution to journalArticle

Abstract

The definition of human immunodeficiency virus type 1 (HIV-1) immunogenic epitopes is central to the rational design of AIDS vaccine strategies. In this study, we have generated seven HIV-1 reverse transcriptase-specific cytotoxic T-lymphocyte (CTL) clones from the peripheral blood of two seropositive subjects. Epitopes recognized by these CTL clones were identified by using target cells infected with recombinant HIV-1 - vaccinia virus vectors expressing truncated reverse transcriptase proteins and further defined by using target cells incubated with overlapping 25-amino acid synthetic reverse transcriptase peptides. Five different CTL epitopes were identified, and in each case recognition was restricted by class I human leukocyte antigens (HLA). Clones maintained specific cytolytic function in continuous culture for up to 11 months, requiring only periodic restimulation with a CD3-specific monoclonal antibody. These results indicate that HIV-1-specific, major histocompatibility class I-restricted CTL recognize multiple epitopes of a single viral gene product in conjunction with different host HLA antigens. In addition, they demonstrate that human virus-specific CTL can be grown in long-term culture without the need for reexposure to viral antigen.

Original languageEnglish (US)
Pages (from-to)9514-9518
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume86
Issue number23
DOIs
StatePublished - Dec 22 1989
Externally publishedYes

Keywords

  • AIDS
  • cell-mediated immunity
  • immunogenic viral epitopes
  • reverse transcriptase

ASJC Scopus subject areas

  • General

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