Document 0402
 DOCN  M9550402
 TI    Insertion of a short human immunodeficiency virus (HIV)-2 gp36 sequence
       into an HIV-1 p24 recombinant protein results in a polypeptide with
       potent and TCRBV-restricted T cell triggering activity.
 DT    9505
 AU    Imberti L; Sottini A; Quiros Roldan E; Albertini A; Mattioli S; Prati E;
       Primi D; III Laboratorio Analisi, Spedali Civili, Brescia, Italy.
 SO    Eur J Immunol. 1995 Jan;25(1):218-25. Unique Identifier : AIDSLINE
       MED/95145530
 AB    In the present work we investigate whether artificial alterations of the
       structure of an inactive retrovirus-encoded protein could transform it
       in a superantigen. As a model system we used a recombinant human
       immunodeficiency virus (HIV)-1 p24 protein and two of its variants in
       which a short peptide corresponding to sequences of gp41 of HIV-1 (HIV-1
       p24*) or gp36 of HIV-2 (HIV-1-2 p24*) has been inserted nearby the
       carboxy-terminal end of HIV-1 p24. As expected both HIV-1 p24 and HIV-1
       p24* were inactive, while HIV-1-2 p24* was a potent inducer of human,
       but not murine, T cell proliferation. The possibility that the observed
       activity was due to contaminants was ruled out since the proliferative
       response could be specifically inhibited by a monoclonal anti-p24
       antibody and by a peptide encompassing the area of HIV-1 p24/HIV-2 gp36
       junction. Furthermore, the data exclude the possibility that the gp36
       insertion is per se responsible for the observed proliferative activity.
       The analysis of the functional, phenotypic and molecular properties of
       the responding cells demonstrated that the response was class II
       dependent and that the activated cells were predominantly CD4+CD8-
       expressing a strongly biased repertoire of TCRBV segments. Collectively,
       these data strongly suggest that the HIV-1-2 p24* fusion protein shares
       common functional properties typical of superantigen molecules. Thus,
       our demonstration that a viral protein can be transformed into a
       superantigen simply by the insertion of a short peptide at the
       carboxy-terminal end has important implications for understanding the
       mode of action of retrovirus-encoded superantigens.
 DE    Amino Acid Sequence  Base Sequence  Cells, Cultured  Cloning, Molecular
       Gene Products, env/CHEMISTRY/*IMMUNOLOGY  Human  HIV
       Antigens/CHEMISTRY/*IMMUNOLOGY  HIV Core Protein
       p24/CHEMISTRY/*IMMUNOLOGY  HIV-1/IMMUNOLOGY  HIV-2/IMMUNOLOGY
       Immunophenotyping  Lymphocyte Transformation/IMMUNOLOGY  Molecular
       Sequence Data  Polymerase Chain Reaction  Receptors, Antigen, T-Cell,
       alpha-beta/GENETICS/IMMUNOLOGY  Recombinant Fusion
       Proteins/CHEMISTRY/IMMUNOLOGY  Support, Non-U.S. Gov't
       T-Lymphocytes/*IMMUNOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).