       Document 0523
 DOCN  M9590523
 TI    Human T helper cells specific for HIV reverse transcriptase: possible
       role in intrastructural help for HIV envelope-specific antibodies.
 DT    9509
 AU    Manca F; Fenoglio D; Valle MT; Li Pira G; Kunkl A; Balderas RS; Baccala
       RG; Kono DH; Ferraris A; Saverino D; et al; Department of Immunology,
       San Martino Hospital, University of; Genoa, Italy.
 SO    Eur J Immunol. 1995 May;25(5):1217-23. Unique Identifier : AIDSLINE
       MED/95293014
 AB    Cooperation between B cells specific for an antigen exposed on a viral
       structure and T helper (Th) cells specific for an internal antigen, as
       demonstrated with influenza, hepatitis B and rabies viruses, has been
       termed intrastructural help. Th cells specific for internal proteins of
       HIV, which are much less mutated than its exposed antigens, may be
       valuable in vaccine design against this virus. We investigated the human
       Th repertoire specific for the core HIV antigen reverse transcriptase
       (p66), and determined whether these cells could be candidate
       intrastructural T helpers. CD4+ T lines and clones were generated from
       non-immune individuals by stimulation with p66-pulsed antigen-presenting
       cells (APC). Specific lines were obtained with p66 from 19 out of 21
       (90%) of these individuals, vs. 7 out of 29 (24%) with gp120. Diverse
       epitopes were recognized by different individuals, and various V beta
       genes were used by these clones. Clones using the same V beta genes were
       of diverse origin, according to VDJ region sequence. Of these lines 45%
       responded to p66 in the context of HIV virions. Moreover, p66-specific
       clones could respond to APC that had internalized HIV complexed with
       envelope-specific monoclonal antibodies, suggesting that p66-specific Th
       cells may participate in intrastructural help. These studies indicate
       that p66-specific Th cells are detectable in vitro in most naive
       individuals and exhibit clonal heterogeneity, and that the majority
       recognize an HIV conserved antigen. They respond to p66 following
       processing of whole virions and are clearly candidates for
       intrastructural help. If confirmed in vivo, p66 should be included among
       vaccine candidates investigated to optimize the anti-HIV Th response.
 DE    Amino Acid Sequence  Antigen-Presenting Cells  Antigens,
       Surface/*IMMUNOLOGY  B-Lymphocyte Subsets/*IMMUNOLOGY  Base Sequence
       Cell Line  Clone Cells  Comparative Study  CD4-Positive
       T-Lymphocytes/*IMMUNOLOGY  Gene Rearrangement, beta-Chain T-Cell Antigen
       Receptor  Human  HIV Antibodies/*IMMUNOLOGY  HIV Antigens/*IMMUNOLOGY
       *Lymphocyte Cooperation  Molecular Sequence Data  Receptors, Antigen,
       T-Cell, alpha-beta/GENETICS  Reverse Transcriptase/*IMMUNOLOGY  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.
       Virion/IMMUNOLOGY/ULTRASTRUCTURE  JOURNAL ARTICLE

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

