Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.
HIV type 1 envelope glycoprotein 120 carboxy-terminal peptide-induced human T cell lines selectively suppress heterogeneous proliferative T cell responses to soluble antigens.
AIDS Res Hum Retroviruses. 1997 Oct 10;13(15):1313-24. Unique Identifier : AIDSLINE MED/97479767 Wilson SE; Habeshaw JA; Addawe MA; Hounsell EF; Oxford JS; Academic Virology, The London Hospital Medical College, UK.; swilson@hivnet.fhcrc.org
Abstract:
It has been proposed that the highly conserved human immunodeficiency virus type 1 (HIV-1) envelope gp120 carboxy-terminal sequence, TKAKRRVVEREKR (CT120), may represent a functional mimic of the human leukocyte antigen (HLA) class II DR beta-chain third hypervariable region (HVR3) sequence motif located at position 69-81. Presentation of this potentially pathogenic fragment by HLA class I and/or II molecules, in a manner analogous to the indirect pathway of allorecognition, may induce both widespread cellular activation and also break self-tolerance, resulting in the selective and progressive anti-self HLA class II-directed immune suppression, which is a central feature of HIV-1 infection and the associated acquired immune deficiency syndrome (AIDS). To investigate the functional role of the HIV-1 gp120 C-terminal fragment T cell lines (TCLs) were raised from three healthy HIV-1-seronegative subjects at low risk of HIV-1 exposure, by repeated stimulation with a short synthetic 13-mer CT120 peptide in vitro. Graded concentrations (10[3] to 5 x 10[4]) of CT120 TCLs suppressed the primary 6-day proliferation of autologous PBMCs in response to the soluble antigens tetanus toxoid (TT) and purified protein derivative (PPD). In contrast, CT120 TCLs demonstrated no suppressive effect on 3-day phytohemagglutinin (PHA), concanavalin A (ConA), and pokeweed mitogen (PWM) mitogenic responses. Fractionation of CT120 TCLs into highly purified CD4+ and CD8+ T cell subsets demonstrated that the CD8+ T cell fraction mediated the suppressor effector function. HLA restriction analysis revealed a complex pattern as both anti-HLA class II DR and anti-HLA class I (A, B, C) MAbs inhibited proliferation of oligoclonal CD8+ CT120 TCLs. Strategies aimed at specifically inhibiting such putative immunopathogenic HIV-1-encoded T cell epitopes may be an important consideration for development of future HIV-1 immunotherapy.
Keywords: Adult Amino Acid Sequence Antibodies, Blocking/IMMUNOLOGY Autoimmunity Cell Division Cells, Cultured Concanavalin A/IMMUNOLOGY Cross Reactions/IMMUNOLOGY CD8-Positive T-Lymphocytes/IMMUNOLOGY Dose-Response Relationship, Immunologic Epitope Mapping Epitopes/IMMUNOLOGY Histocompatibility Antigens Class I/IMMUNOLOGY Histocompatibility Antigens Class II/IMMUNOLOGY Histocompatibility Testing Human HIV Envelope Protein gp120/*IMMUNOLOGY HIV Infections/*IMMUNOLOGY HIV Seronegativity HIV-1/*IMMUNOLOGY Immune Tolerance Leukocytes, Mononuclear/IMMUNOLOGY Middle Age Molecular Sequence Data Peptides/CHEMICAL SYNTHESIS/*IMMUNOLOGY Phytohemagglutinins/IMMUNOLOGY Pokeweed Mitogens/IMMUNOLOGY Support, Non-U.S. Gov't T-Lymphocyte Subsets/IMMUNOLOGY T-Lymphocytes/CYTOLOGY/*IMMUNOLOGY Tetanus Toxoid/IMMUNOLOGY Tuberculin/IMMUNOLOGY JOURNAL ARTICLE
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Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.
