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).