HIV type 1 envelope glycoprotein 120 carboxy-terminal peptide-induced human T cell lines selectively suppress heterogeneous proliferative T cell responses to soluble antigens

• Published in: AIDS research and human retroviruses Vol. 13; no. 15; p. 1313
• Main Authors: Wilson, S E, Habeshaw, J A, Addawe, M A, Hounsell, E F, Oxford, J S
• Format: Journal Article
• Language: English
• Published: United States 10.10.1997
• Subjects: Adult; Amino Acid Sequence; Antibodies, Blocking - immunology; Autoimmunity; CD8-Positive T-Lymphocytes - immunology; Cell Division; Cells, Cultured; Concanavalin A - immunology; Cross Reactions - immunology; Dose-Response Relationship, Immunologic; Epitope Mapping; Epitopes - immunology; Histocompatibility Antigens Class I - immunology; Histocompatibility Antigens Class II - immunology; Histocompatibility Testing; HIV Envelope Protein gp120 - immunology; HIV Infections - immunology; HIV Seronegativity; HIV-1 - immunology; Humans; Immune Tolerance; Leukocytes, Mononuclear - immunology; Middle Aged; Molecular Sequence Data; Peptides - chemical synthesis; Peptides - immunology; Phytohemagglutinins - immunology; Pokeweed Mitogens - immunology; T-Lymphocyte Subsets - immunology; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Tetanus Toxoid - immunology; Tuberculin - immunology
• ISSN: 0889-2229
• DOI: 10.1089/aid.1997.13.1313

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.