Highly stable oligomerization forms of HIV-1 Tat detected by monoclonal antibodies and requirement of monomeric forms for the transactivating function on the HIV-1 LTR

Giovanna Tosi, Raffaella Meazza, Andrea De Lerma Barbaro, Antonella D'Agostino, Stefania Mazza, Giampietro Corradin, Adriana Albini, Douglas M. Noonan, Silvano Ferrini, Roberto S. Accolla

Research output: Contribution to journalArticle

Abstract

The use of newly generated murine monoclonal antibodies directed against distinct epitopes of a functionally active, chemically synthesized HIV-1 Tat protein has permitted the identification of several molecular forms including monomers, dimers and trimers. Dimers and trimers are particularly stable and resistant to strong reducing conditions. Through epitope mapping it has been possible to demonstrate that the major immunodominant epitope is contained within the basic region of the Tat protein and is lost after oligomerization of the molecule. In contrast, N-terminal, C-terminal and conformation-dependent epitopes are still accessible to mAb specific recognition after Tat oligomerization. Moreover, by using a quantitative HIV-LTR transactivation assay depending upon exogenous Tat, we could extrapolate the amount of functional Tat produced by cell lines stably transfected with the viral transactivator. More importantly, we could show that only the monomeric form of exogenous Tat is the relevant functional form acting in cells harbouring the HIV-1 LTR promoter.

Original languageEnglish
Pages (from-to)1120-1126
Number of pages7
JournalEuropean Journal of Immunology
Volume30
Issue number4
DOIs
Publication statusPublished - 2000

Keywords

  • Epitope mapping
  • HIV-1 Tat
  • Molecular heterogeneity
  • Monoclonal antibody

ASJC Scopus subject areas

  • Immunology

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